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Yorodumi- EMDB-20530: Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP a... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20530 | |||||||||
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Title | Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP and glibenclamide | |||||||||
Map data | SUR1-GBC-ATP state | |||||||||
Sample |
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Function / homology | Function and homology information Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / sulfonylurea receptor activity / cell body fiber / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade ...Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / sulfonylurea receptor activity / cell body fiber / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ATPase-coupled monoatomic cation transmembrane transporter activity / inward rectifier potassium channel activity / nervous system process / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / response to stress / ankyrin binding / Ion homeostasis / response to ATP / action potential / potassium ion import across plasma membrane / response to testosterone / regulation of insulin secretion / voltage-gated potassium channel activity / intercalated disc / potassium channel activity / ABC-type transporter activity / axolemma / negative regulation of insulin secretion / cellular response to nutrient levels / heat shock protein binding / potassium ion transmembrane transport / T-tubule / acrosomal vesicle / regulation of membrane potential / determination of adult lifespan / response to ischemia / positive regulation of protein localization to plasma membrane / cellular response to glucose stimulus / potassium ion transport / sarcolemma / cellular response to nicotine / glucose metabolic process / cellular response to tumor necrosis factor / response to estradiol / nuclear envelope / presynaptic membrane / transmembrane transporter binding / response to hypoxia / endosome / response to xenobiotic stimulus / neuronal cell body / glutamatergic synapse / apoptotic process / ATP hydrolysis activity / ATP binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Cricetus cricetus (black-bellied hamster) / Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.74 Å | |||||||||
Authors | Shyng SL / Yoshioka C / Martin GM / Sung MW | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Elife / Year: 2019 Title: Mechanism of pharmacochaperoning in a mammalian K channel revealed by cryo-EM. Authors: Gregory M Martin / Min Woo Sung / Zhongying Yang / Laura M Innes / Balamurugan Kandasamy / Larry L David / Craig Yoshioka / Show-Ling Shyng / Abstract: ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β- ...ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse K inhibitors are known to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of a mammalian K channel bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. We found all three drugs bind within a common pocket in SUR1. Further, we found the N-terminus of Kir6.2 inserted within the central cavity of the SUR1 ABC core, adjacent the drug binding pocket. The findings reveal a common mechanism by which diverse compounds stabilize the Kir6.2 N-terminus within SUR1's ABC core, allowing it to act as a firm 'handle' for the assembly of metastable mutant SUR1-Kir6.2 complexes. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20530.map.gz | 7.8 MB | EMDB map data format | |
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Header (meta data) | emd-20530-v30.xml emd-20530.xml | 14.3 KB 14.3 KB | Display Display | EMDB header |
Images | emd_20530.png | 176.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20530 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20530 | HTTPS FTP |
-Validation report
Summary document | emd_20530_validation.pdf.gz | 339.9 KB | Display | EMDB validaton report |
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Full document | emd_20530_full_validation.pdf.gz | 339.4 KB | Display | |
Data in XML | emd_20530_validation.xml.gz | 4.3 KB | Display | |
Data in CIF | emd_20530_validation.cif.gz | 4.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20530 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20530 | HTTPS FTP |
-Related structure data
Related structure data | 6pzaMC 6pz9C 6pzbC 6pzcC 6pziC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20530.map.gz / Format: CCP4 / Size: 38.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | SUR1-GBC-ATP state | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.855 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : KATP-RPG-ATP
Entire | Name: KATP-RPG-ATP |
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Components |
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-Supramolecule #1: KATP-RPG-ATP
Supramolecule | Name: KATP-RPG-ATP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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-Supramolecule #2: SUR1
Supramolecule | Name: SUR1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Cricetus cricetus (black-bellied hamster) |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) / Recombinant cell: INS - 1 cells clone 832/13 |
-Supramolecule #3: KNtp
Supramolecule | Name: KNtp / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) |
-Macromolecule #1: ATP-binding cassette sub-family C member 8
Macromolecule | Name: ATP-binding cassette sub-family C member 8 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Cricetus cricetus (black-bellied hamster) |
Molecular weight | Theoretical: 177.333578 KDa |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) |
Sequence | String: MPLAFCGTEN HSAAYRVDQG VLNNGCFVDA LNVVPHVFLL FITFPILFIG WGSQSSKVHI HHSTWLHFPG HNLRWILTFI LLFVLVCEI AEGILSDGVT ESRHLHLYMP AGMAFMAAIT SVVYYHNIET SNFPKLLIAL LIYWTLAFIT KTIKFVKFYD H AIGFSQLR ...String: MPLAFCGTEN HSAAYRVDQG VLNNGCFVDA LNVVPHVFLL FITFPILFIG WGSQSSKVHI HHSTWLHFPG HNLRWILTFI LLFVLVCEI AEGILSDGVT ESRHLHLYMP AGMAFMAAIT SVVYYHNIET SNFPKLLIAL LIYWTLAFIT KTIKFVKFYD H AIGFSQLR FCLTGLLVIL YGMLLLVEVN VIRVRRYIFF KTPREVKPPE DLQDLGVRFL QPFVNLLSKG TYWWMNAFIK TA HKKPIDL RAIAKLPIAM RALTNYQRLC VAFDAQARKD TQSPQGARAI WRALCHAFGR RLILSSTFRI LADLLGFAGP LCI FGIVDH LGKENHVFQP KTQFLGVYFV SSQEFLGNAY VLAVLLFLAL LLQRTFLQAS YYVAIETGIN LRGAIQTKIY NKIM HMSTS NLSMGEMTAG QICNLVAIDT NQLMWFFFLC PNLWTMPVQI IVGVILLYYI LGVSALIGAA VIILLAPVQY FVATK LSQA QRTTLEHSNE RLKQTNEMLR GMKLLKLYAW ESIFCSRVEV TRRKEMTSLR AFAVYTSISI FMNTAIPIAA VLITFV GHV SFFKESDLSP SVAFASLSLF HILVTPLFLL SSVVRSTVKA LVSVQKLSEF LSSAEIREEQ CAPREPAPQG QAGKYQA VP LKVVNRKRPA REEVRDLLGP LQRLAPSMDG DADNFCVQII GGFFTWTPDG IPTLSNITIR IPRGQLTMIV GQVGCGKS S LLLATLGEMQ KVSGAVFWNS NLPDSEGEDP SSPERETAAG SDIRSRGPVA YASQKPWLLN ATVEENITFE SPFNKQRYK MVIEACSLQP DIDILPHGDQ TQIGERGINL SGGQRQRISV ARALYQQTNV VFLDDPFSAL DVHLSDHLMQ AGILELLRDD KRTVVLVTH KLQYLPHADW IIAMKDGTIQ REGTLKDFQR SECQLFEHWK TLMNRQDQEL EKETVMERKA SEPSQGLPRA M SSRDGLLL DEEEEEEEAA ESEEDDNLSS VLHQRAKIPW RACTKYLSSA GILLLSLLVF SQLLKHMVLV AIDYWLAKWT DS ALVLSPA ARNCSLSQEC DLDQSVYAMV FTLLCSLGIV LCLVTSVTVE WTGLKVAKRL HRSLLNRIIL APMRFFETTP LGS ILNRFS SDCNTIDQHI PSTLECLSRS TLLCVSALTV ISYVTPVFLV ALLPLAVVCY FIQKYFRVAS RDLQQLDDTT QLPL VSHFA ETVEGLTTIR AFRYEARFQQ KLLEYTDSNN IASLFLTAAN RWLEVCMEYI GACVVLIAAA TSISNSLHRE LSAGL VGLG LTYALMVSNY LNWMVRNLAD MEIQLGAVKR IHALLKTEAE SYEGLLAPSL IPKNWPDQGK IQIQNLSVRY DSSLKP VLK HVNTLISPGQ KIGICGRTGS GKSSFSLAFF RMVDMFEGRI IIDGIDIAKL PLHTLRSRLS IILQDPVLFS GTIRFNL DP EKKCSDSTLW EALEIAQLKL VVKALPGGLD AIITEGGENF SQGQRQLFCL ARAFVRKTSI FIMDEATASI DMATENIL Q KVVMTAFADR TVVTIAHRVH TILSADLVMV LKRGAILEFD KPETLLSQKD SVFASFVRAD K |
-Macromolecule #2: ATP-sensitive inward rectifier potassium channel 11
Macromolecule | Name: ATP-sensitive inward rectifier potassium channel 11 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 43.645719 KDa |
Recombinant expression | Organism: Rattus norvegicus (Norway rat) |
Sequence | String: MLSRKGIIPE EYVLTRLAED PTEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMV WWLIAFAHGD LAPGEGTNVP CVTSIHSFSS AFLFSIEVQV TIGFGGRMVT EECPLAILIL IVQNIVGLMI N AIMLGCIF ...String: MLSRKGIIPE EYVLTRLAED PTEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMV WWLIAFAHGD LAPGEGTNVP CVTSIHSFSS AFLFSIEVQV TIGFGGRMVT EECPLAILIL IVQNIVGLMI N AIMLGCIF MKTAQAHRRA ETLIFSKHAV ITPRHGRLCF MLRVGDLRKS MIISATIHMQ VVRKTTSPEG EVVPLHQVDI PM ENGVGGN SIFLVAPLII YHVIDSNSPL YDLAPSDLHH HQDLEIIVIL EGVVETTGIT TQARTSYLAD EILWGQRFVP IVA EEDGRY SVDYSKFGNT VKVPTPLCTA RQLDEDRSLL DALTLASSRG PLRKRSVAVA KAKPKFSISP DSLS |
-Macromolecule #3: 5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-...
Macromolecule | Name: 5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-methoxybenzamide type: ligand / ID: 3 / Number of copies: 1 / Formula: GBM |
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Molecular weight | Theoretical: 494.004 Da |
Chemical component information | ChemComp-GBM: |
-Macromolecule #4: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 1 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ChemComp-ATP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.74 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 171420 |
Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: ANGULAR RECONSTITUTION |