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- EMDB-21456: Cryo-EM structure of M1214_N1 Fab in complex with CH505 TF chimer... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21456 | ||||||||||||
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Title | Cryo-EM structure of M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer | ||||||||||||
![]() | M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer | ||||||||||||
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Function / homology | ![]() : / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane ...: / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.86 Å | ||||||||||||
![]() | Chan K-W / Kong XP | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA. Authors: Manxue Jia / Rachel A Liberatore / Yicheng Guo / Kun-Wei Chan / Ruimin Pan / Hong Lu / Eric Waltari / Eva Mittler / Kartik Chandran / Andrés Finzi / Daniel E Kaufmann / Michael S Seaman / ...Authors: Manxue Jia / Rachel A Liberatore / Yicheng Guo / Kun-Wei Chan / Ruimin Pan / Hong Lu / Eric Waltari / Eva Mittler / Kartik Chandran / Andrés Finzi / Daniel E Kaufmann / Michael S Seaman / David D Ho / Lawrence Shapiro / Zizhang Sheng / Xiang-Peng Kong / Paul D Bieniasz / Xueling Wu / ![]() ![]() Abstract: The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env ...The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability. | ||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 167.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.9 KB 17.9 KB | Display Display | ![]() |
Images | ![]() | 38.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6vy2MC ![]() 6vu2C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.16 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer
Entire | Name: M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer |
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Components |
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-Supramolecule #1: M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer
Supramolecule | Name: M1214_N1 Fab in complex with CH505 TF chimeric SOSIP.664 Env trimer type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: chimeric CH505TF SOSIP664.R6 E64K A316W
Supramolecule | Name: chimeric CH505TF SOSIP664.R6 E64K A316W / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: Fab fragment of the M1214_N1 IgG
Supramolecule | Name: Fab fragment of the M1214_N1 IgG / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Glycoprotein 120
Macromolecule | Name: Glycoprotein 120 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 54.540402 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPMGSLQPLA TLYLLGMLVA SVLAAENLWV TVYYGVPVWK EAKTTLFCAS DAKAYEKKVH NVWATHACVP TDPNPQEMVL KNVTENFNM WKNDMVDQMH EDVISLWDQS LKPCVKLTPL CVTLNCTNAT ASNSSIIEGM KNCSFNITTE LRDKREKKNA L FYKLDIVQ ...String: MPMGSLQPLA TLYLLGMLVA SVLAAENLWV TVYYGVPVWK EAKTTLFCAS DAKAYEKKVH NVWATHACVP TDPNPQEMVL KNVTENFNM WKNDMVDQMH EDVISLWDQS LKPCVKLTPL CVTLNCTNAT ASNSSIIEGM KNCSFNITTE LRDKREKKNA L FYKLDIVQ LDGNSSQYRL INCNTSVITQ ACPKVSFDPI PIHYCAPAGY AILKCNNKTF TGTGPCNNVS TVQCTHGIKP VV STQLLLN GSLAEGEIII RSENITNNVK TIIVHLNESV KIECTRPNNK TRTSIRIGPG QWFYATGQVI GDIREAYCNI NES KWNETL QRVSKKLKEY FPHKNITFQP SSGGDLEITT HSFNCGGEFF YCNTSSLFNR TYMANSTDMA NSTETNSTRT ITIH CRIKQ IINMWQEVGR AMYAPPIAGN ITCISNITGL LLTRDGGKNN TETFRPGGGN MKDNWRSELY KYKVVKIEPL GVAPT RCKR RVV |
-Macromolecule #2: Glycoprotein 41
Macromolecule | Name: Glycoprotein 41 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 18.146699 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GRRRRRRAVG IGAVFLGFLG AAGSTMGAAS MTLTVQARNL LSGIVQQQSN LLRAPEAQQH LLKLTVWGIK QLQARVLAVE RYLRDQQLL GIWGCSGKLI CCTNVPWNSS WSNRNLSEIW DNMTWLQWDK EISNYTQIIY GLLEESQNQQ EKNEQDLLAL D |
-Macromolecule #3: M1214 N1 Fab heavy chain
Macromolecule | Name: M1214 N1 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.210143 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DRLFQSGGGV SRPGGSLRVN CGASGFTVRT HYMYWLRQSP GKGLEWVAFM NSGGSVSYVD SVRGRFSVSR DNPANAMVLQ MDALKIEDT GTYYCARELR EAWYGDLRDY SGLDVWGRGT IVSISSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: DRLFQSGGGV SRPGGSLRVN CGASGFTVRT HYMYWLRQSP GKGLEWVAFM NSGGSVSYVD SVRGRFSVSR DNPANAMVLQ MDALKIEDT GTYYCARELR EAWYGDLRDY SGLDVWGRGT IVSISSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPK |
-Macromolecule #4: M1214 N1 Fab light chain
Macromolecule | Name: M1214 N1 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 22.87642 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSALAQPPSV SGSPGQSVTI TCTGINDYGA AYKFVSWYQQ HPGKEPRLIM KNVKDRWSVT PNRFSGSTSG NTASLTISNL QSDDEAQYF CAVYAGGFTF PRLGGGTKLS VLSQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT ...String: QSALAQPPSV SGSPGQSVTI TCTGINDYGA AYKFVSWYQQ HPGKEPRLIM KNVKDRWSVT PNRFSGSTSG NTASLTISNL QSDDEAQYF CAVYAGGFTF PRLGGGTKLS VLSQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT PSKQSNNKYA ASSYLSLTPE QWKSHRSYSC QVTHEGSTVE KTVAPT |
-Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 24 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |