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Structure paper

Title	Time-resolved cryo-EM of G-protein activation by a GPCR.
Journal, issue, pages	Nature, Year 2024
Publish date	Mar 13, 2024
Authors	Makaía M Papasergi-Scott / Guillermo Pérez-Hernández / Hossein Batebi / Yang Gao / Gözde Eskici / Alpay B Seven / Ouliana Panova / Daniel Hilger / Marina Casiraghi / Feng He / Luis Maul / Peter Gmeiner / Brian K Kobilka / Peter W Hildebrand / Georgios Skiniotis /
PubMed Abstract	G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Gα subunit. To visualize this mechanism, we developed a time-resolved cryo-EM ...G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Gα subunit. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines the progression of ensembles of pre-steady-state intermediates of a GPCR-G-protein complex. By monitoring the transitions of the stimulatory G protein in complex with the β-adrenergic receptor at short sequential time points after GTP addition, we identified the conformational trajectory underlying G-protein activation and functional dissociation from the receptor. Twenty structures generated from sequential overlapping particle subsets along this trajectory, compared to control structures, provide a high-resolution description of the order of main events driving G-protein activation in response to GTP binding. Structural changes propagate from the nucleotide-binding pocket and extend through the GTPase domain, enacting alterations to Gα switch regions and the α5 helix that weaken the G-protein-receptor interface. Molecular dynamics simulations with late structures in the cryo-EM trajectory support that enhanced ordering of GTP on closure of the α-helical domain against the nucleotide-bound Ras-homology domain correlates with α5 helix destabilization and eventual dissociation of the G protein from the GPCR. These findings also highlight the potential of time-resolved cryo-EM as a tool for mechanistic dissection of GPCR signalling events.
External links	Nature / PubMed:38480881
Methods	EM (single particle)
Resolution	2.9 - 4.2 Å
Structure data	29951 8gdz EMDB-29951, PDB-8gdz: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#1 of 20) Method: EM (single particle) / Resolution: 3.5 Å 29952 8ge1 EMDB-29952, PDB-8ge1: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#2 of 20) Method: EM (single particle) / Resolution: 3.4 Å 29953 8ge2 EMDB-29953, PDB-8ge2: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#3 of 20) Method: EM (single particle) / Resolution: 3.3 Å 29954 8ge3 EMDB-29954, PDB-8ge3: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#4 of 20) Method: EM (single particle) / Resolution: 3.3 Å 29955 8ge4 EMDB-29955, PDB-8ge4: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#5 of 20) Method: EM (single particle) / Resolution: 3.3 Å 29956 8ge5 EMDB-29956, PDB-8ge5: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#6 of 20) Method: EM (single particle) / Resolution: 3.2 Å 29958 8ge6 EMDB-29958, PDB-8ge6: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#7 of 20) Method: EM (single particle) / Resolution: 3.4 Å 29959 8ge7 EMDB-29959, PDB-8ge7: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#8 of 20) Method: EM (single particle) / Resolution: 3.4 Å 29960 8ge8 EMDB-29960, PDB-8ge8: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#9 of 20) Method: EM (single particle) / Resolution: 3.4 Å 29961 8ge9 EMDB-29961, PDB-8ge9: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#10 of 20) Method: EM (single particle) / Resolution: 3.5 Å 29962 8gea EMDB-29962, PDB-8gea: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#11 of 20) Method: EM (single particle) / Resolution: 3.5 Å 29964 8geb EMDB-29964, PDB-8geb: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#12 of 20) Method: EM (single particle) / Resolution: 3.6 Å 29965 8gec EMDB-29965, PDB-8gec: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#13 of 20) Method: EM (single particle) / Resolution: 3.5 Å 29966 8ged EMDB-29966, PDB-8ged: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#14 of 20) Method: EM (single particle) / Resolution: 3.5 Å 29967 8gee EMDB-29967, PDB-8gee: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#15 of 20) Method: EM (single particle) / Resolution: 3.7 Å 29968 8gef EMDB-29968, PDB-8gef: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#16 of 20) Method: EM (single particle) / Resolution: 3.8 Å 29969 8geg EMDB-29969, PDB-8geg: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#17 of 20) Method: EM (single particle) / Resolution: 3.8 Å 29970 8geh EMDB-29970, PDB-8geh: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#18 of 20) Method: EM (single particle) / Resolution: 4.0 Å 29971 8gei EMDB-29971, PDB-8gei: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#19 of 20) Method: EM (single particle) / Resolution: 4.1 Å 29972 8gej EMDB-29972, PDB-8gej: CryoEM structure of beta-2-adrenergic receptor in complex with nucleotide-free Gs heterotrimer (#20 of 20) Method: EM (single particle) / Resolution: 4.2 Å 29985 8gfv EMDB-29985, PDB-8gfv: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #1 of 20) Method: EM (single particle) / Resolution: 3.1 Å 29986 8gfw EMDB-29986, PDB-8gfw: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #2 of 20) Method: EM (single particle) / Resolution: 3.0 Å 29987 8gfx EMDB-29987, PDB-8gfx: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #3 of 20) Method: EM (single particle) / Resolution: 3.0 Å 29988 8gfy EMDB-29988, PDB-8gfy: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #4 of 20) Method: EM (single particle) / Resolution: 3.0 Å 29989 8gfz EMDB-29989, PDB-8gfz: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #5 of 20) Method: EM (single particle) / Resolution: 3.0 Å 29990 8gg0 EMDB-29990, PDB-8gg0: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #6 of 20) Method: EM (single particle) / Resolution: 2.9 Å 29991 8gg1 EMDB-29991, PDB-8gg1: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #7 of 20) Method: EM (single particle) / Resolution: 3.0 Å 29992 8gg2 EMDB-29992, PDB-8gg2: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #8 of 20) Method: EM (single particle) / Resolution: 3.0 Å 29993 8gg3 EMDB-29993, PDB-8gg3: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #9 of 20) Method: EM (single particle) / Resolution: 3.1 Å 29994 8gg4 EMDB-29994, PDB-8gg4: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #10 of 20) Method: EM (single particle) / Resolution: 3.2 Å 29995 8gg5 EMDB-29995, PDB-8gg5: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #11 of 20) Method: EM (single particle) / Resolution: 3.2 Å 29996 8gg6 EMDB-29996, PDB-8gg6: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #12 of 20) Method: EM (single particle) / Resolution: 3.3 Å 29997 8gg7 EMDB-29997, PDB-8gg7: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #13 of 20) Method: EM (single particle) / Resolution: 3.3 Å 29998 8gg8 EMDB-29998, PDB-8gg8: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #14 of 20) Method: EM (single particle) / Resolution: 3.3 Å 29999 8gg9 EMDB-29999, PDB-8gg9: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #15 of 20) Method: EM (single particle) / Resolution: 3.4 Å 40000 8gga EMDB-40000, PDB-8gga: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #16 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40001 8ggb EMDB-40001, PDB-8ggb: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #17 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40002 8ggc EMDB-40002, PDB-8ggc: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #18 of 20) Method: EM (single particle) / Resolution: 3.4 Å 40004 8gge EMDB-40004, PDB-8gge: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #19 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40005 8ggf EMDB-40005, PDB-8ggf: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #20 of 20) Method: EM (single particle) / Resolution: 3.6 Å 40009 8ggi EMDB-40009, PDB-8ggi: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #1 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40010 8ggj EMDB-40010, PDB-8ggj: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #2 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40011 8ggk EMDB-40011, PDB-8ggk: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #3 of 20) Method: EM (single particle) / Resolution: 3.3 Å 40012 8ggl EMDB-40012, PDB-8ggl: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #4 of 20) Method: EM (single particle) / Resolution: 3.2 Å 40013 8ggm EMDB-40013, PDB-8ggm: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #5 of 20) Method: EM (single particle) / Resolution: 3.2 Å 40014 8ggn EMDB-40014, PDB-8ggn: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #6 of 20) Method: EM (single particle) / Resolution: 3.3 Å 40015 8ggo EMDB-40015, PDB-8ggo: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #7 of 20) Method: EM (single particle) / Resolution: 3.2 Å 40016 8ggp EMDB-40016, PDB-8ggp: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #8 of 20) Method: EM (single particle) / Resolution: 3.2 Å 40017 8ggq EMDB-40017, PDB-8ggq: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #9 of 20) Method: EM (single particle) / Resolution: 3.4 Å 40018 8ggr EMDB-40018, PDB-8ggr: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #10 of 20) Method: EM (single particle) / Resolution: 3.4 Å 40019 8ggs EMDB-40019, PDB-8ggs: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #11 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40020 8ggt EMDB-40020, PDB-8ggt: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #12 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40021 8ggu EMDB-40021, PDB-8ggu: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #13 of 20) Method: EM (single particle) / Resolution: 3.4 Å 40022 8ggv EMDB-40022, PDB-8ggv: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #14 of 20) Method: EM (single particle) / Resolution: 3.5 Å 40023 8ggw EMDB-40023, PDB-8ggw: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #15 of 20) Method: EM (single particle) / Resolution: 3.6 Å 40024 8ggx EMDB-40024, PDB-8ggx: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #16 of 20) Method: EM (single particle) / Resolution: 3.6 Å 40025 8ggy EMDB-40025, PDB-8ggy: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #17 of 20) Method: EM (single particle) / Resolution: 3.9 Å 40026 8ggz EMDB-40026, PDB-8ggz: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #18 of 20) Method: EM (single particle) / Resolution: 3.9 Å 40027 8gh0 EMDB-40027, PDB-8gh0: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #19 of 20) Method: EM (single particle) / Resolution: 4.0 Å 40028 8gh1 EMDB-40028, PDB-8gh1: Locally refined cryoEM structure of receptor from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #20 of 20) Method: EM (single particle) / Resolution: 4.1 Å EMDB-40096: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#1 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40097: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#2 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40098: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#3 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40099: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#4 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40100: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#5 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40101: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#6 of 20) Method: EM (single particle) / Resolution: 3.1 Å EMDB-40102: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#7 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40103: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#8 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40104: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#9 of 20) Method: EM (single particle) / Resolution: 3.1 Å EMDB-40105: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#10 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40106: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#11 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40107: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#12 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40108: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#13 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40109: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#14 of 20) Method: EM (single particle) / Resolution: 3.1 Å EMDB-40110: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#15 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40111: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#16 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40112: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#17 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40113: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#18 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40114: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#19 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40115: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 5 sec after GTP addition (#20 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40116: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#1 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40117: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#2 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40118: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#3 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40119: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#4 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40120: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#5 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40121: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#6 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40122: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#7 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40123: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#8 of 20) Method: EM (single particle) / Resolution: 3.5 Å EMDB-40124: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#9 of 20) Method: EM (single particle) / Resolution: 3.6 Å EMDB-40125: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#10 of 20) Method: EM (single particle) / Resolution: 3.6 Å EMDB-40126: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#11 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40127: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#12 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40128: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#13 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40129: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#14 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40130: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#15 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40131: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#16 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40132: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#17 of 20) Method: EM (single particle) / Resolution: 3.9 Å EMDB-40133: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#18 of 20) Method: EM (single particle) / Resolution: 3.9 Å EMDB-40134: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#19 of 20) Method: EM (single particle) / Resolution: 4.0 Å EMDB-40135: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 10 sec after GTP addition (#20 of 20) Method: EM (single particle) / Resolution: 4.1 Å EMDB-40136: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#1 of 20) Method: EM (single particle) / Resolution: 3.5 Å EMDB-40137: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#2 of 20) Method: EM (single particle) / Resolution: 3.5 Å EMDB-40138: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#3 of 20) Method: EM (single particle) / Resolution: 3.5 Å EMDB-40139: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#4 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40140: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#5 of 20) Method: EM (single particle) / Resolution: 3.4 Å EMDB-40141: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#6 of 20) Method: EM (single particle) / Resolution: 3.5 Å EMDB-40142: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#7 of 20) Method: EM (single particle) / Resolution: 3.6 Å EMDB-40143: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#8 of 20) Method: EM (single particle) / Resolution: 3.6 Å EMDB-40144: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#9 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40145: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#10 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40146: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#11 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40147: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#12 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40148: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#13 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40149: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#14 of 20) Method: EM (single particle) / Resolution: 3.8 Å EMDB-40150: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#15 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40151: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#16 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40152: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#17 of 20) Method: EM (single particle) / Resolution: 3.7 Å EMDB-40153: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#18 of 20) Method: EM (single particle) / Resolution: 4.0 Å EMDB-40154: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#19 of 20) Method: EM (single particle) / Resolution: 4.0 Å EMDB-40155: CryoEM structure of beta-2-adrenergic receptor in complex with Gs heterotrimer, 17 sec after GTP addition (#20 of 20) Method: EM (single particle) / Resolution: 4.0 Å EMDB-40156: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #1 of 20) Method: EM (single particle) / Resolution: 3.1 Å EMDB-40157: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #2 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40158: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #3 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40159: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #4 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40160: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #5 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40161: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #6 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40163: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #7 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40164: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #8 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40165: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #9 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40166: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #10 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40167: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #11 of 20) Method: EM (single particle) / Resolution: 3.0 Å EMDB-40168: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #12 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40169: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #13 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40170: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #14 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40171: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #15 of 20) Method: EM (single particle) / Resolution: 3.2 Å EMDB-40172: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #16 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40173: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #17 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40174: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #18 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40175: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #19 of 20) Method: EM (single particle) / Resolution: 3.3 Å EMDB-40176: Locally refined cryoEM structure of G protein heterotrimer from beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (transition intermediate #20 of 20) Method: EM (single particle) / Resolution: 3.4 Å 42408 8unl EMDB-42408, PDB-8unl: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class A) Method: EM (single particle) / Resolution: 3.3 Å 42409 8unm EMDB-42409, PDB-8unm: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class B) Method: EM (single particle) / Resolution: 3.4 Å 42410 8unn EMDB-42410, PDB-8unn: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class C) Method: EM (single particle) / Resolution: 3.4 Å 42411 8uno EMDB-42411, PDB-8uno: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class D) Method: EM (single particle) / Resolution: 3.3 Å 42412 8unp EMDB-42412, PDB-8unp: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class E) Method: EM (single particle) / Resolution: 3.3 Å 42413 8unq EMDB-42413, PDB-8unq: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class F) Method: EM (single particle) / Resolution: 3.3 Å 42414 8unr EMDB-42414, PDB-8unr: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class G) Method: EM (single particle) / Resolution: 3.4 Å 42415 8uns EMDB-42415, PDB-8uns: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class H) Method: EM (single particle) / Resolution: 3.4 Å 42416 8unt EMDB-42416, PDB-8unt: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class I) Method: EM (single particle) / Resolution: 3.4 Å 42417 8unu EMDB-42417, PDB-8unu: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class J) Method: EM (single particle) / Resolution: 3.5 Å 42418 8unv EMDB-42418, PDB-8unv: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class K) Method: EM (single particle) / Resolution: 3.3 Å 42419 8unw EMDB-42419, PDB-8unw: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class L) Method: EM (single particle) / Resolution: 3.4 Å 42420 8unx EMDB-42420, PDB-8unx: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class M) Method: EM (single particle) / Resolution: 3.6 Å 42421 8uny EMDB-42421, PDB-8uny: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class N) Method: EM (single particle) / Resolution: 3.6 Å 42422 8unz EMDB-42422, PDB-8unz: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class O) Method: EM (single particle) / Resolution: 3.8 Å 42423 8uo0 EMDB-42423, PDB-8uo0: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class P) Method: EM (single particle) / Resolution: 3.5 Å 42424 8uo1 EMDB-42424, PDB-8uo1: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class Q) Method: EM (single particle) / Resolution: 3.6 Å 42425 8uo2 EMDB-42425, PDB-8uo2: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class R) Method: EM (single particle) / Resolution: 3.6 Å 42426 8uo3 EMDB-42426, PDB-8uo3: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class S) Method: EM (single particle) / Resolution: 3.5 Å 42427 8uo4 EMDB-42427, PDB-8uo4: CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer (Class T) Method: EM (single particle) / Resolution: 4.0 Å
Chemicals	ChemComp-G1I: (5R,6R)-6-(methylamino)-5,6,7,8-tetrahydronaphthalene-1,2,5-triol ChemComp-HOH: WATER / Water ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM / Guanosine triphosphate ChemComp-MG*: Unknown entry
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN / GPCR / Adrenergic / Receptor / G protein

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