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Yorodumi- EMDB-9787: Structure of pancreatic ATP-sensitive potassium channel bound wit... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9787 | |||||||||||||||
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Title | Structure of pancreatic ATP-sensitive potassium channel bound with repaglinide and ATPgammaS at 3.3A resolution | |||||||||||||||
Map data | the sharpened map from cisTEM | |||||||||||||||
Sample |
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Function / homology | Function and homology information ATP sensitive Potassium channels / response to resveratrol / ATP-activated inward rectifier potassium channel activity / glutamate secretion, neurotransmission / inward rectifying potassium channel / cell body fiber / Regulation of insulin secretion / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade ...ATP sensitive Potassium channels / response to resveratrol / ATP-activated inward rectifier potassium channel activity / glutamate secretion, neurotransmission / inward rectifying potassium channel / cell body fiber / Regulation of insulin secretion / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade / ABC-family proteins mediated transport / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to stress / Ion homeostasis / inward rectifier potassium channel activity / ATPase-coupled monoatomic cation transmembrane transporter activity / nervous system process / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / neuromuscular process / ankyrin binding / response to ATP / response to testosterone / potassium ion import across plasma membrane / action potential / positive regulation of insulin secretion involved in cellular response to glucose stimulus / potassium ion binding / potassium channel activity / intercalated disc / axolemma / ABC-type transporter activity / cellular response to nutrient levels / negative regulation of insulin secretion / T-tubule / heat shock protein binding / positive regulation of protein localization to plasma membrane / potassium ion transport / acrosomal vesicle / response to ischemia / determination of adult lifespan / cellular response to glucose stimulus / sarcolemma / ADP binding / cellular response to nicotine / glucose metabolic process / nuclear envelope / response to estradiol / cellular response to tumor necrosis factor / presynapse / presynaptic membrane / transmembrane transporter binding / endosome / response to hypoxia / response to xenobiotic stimulus / neuronal cell body / glutamatergic synapse / apoptotic process / ATP hydrolysis activity / ATP binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Mus musculus (house mouse) / Mesocricetus auratus (golden hamster) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||
Authors | Chen L / Ding D / Wang M / Wu J-X / Kang Y | |||||||||||||||
Funding support | China, 4 items
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Citation | Journal: Cell Rep / Year: 2019 Title: The Structural Basis for the Binding of Repaglinide to the Pancreatic K Channel. Authors: Dian Ding / Mengmeng Wang / Jing-Xiang Wu / Yunlu Kang / Lei Chen / Abstract: Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium ...Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium channel (K). However, the mechanisms by which RPG binds to the K channel are poorly understood. Here, we describe two cryo-EM structures: the pancreatic K channel in complex with inhibitory RPG and adenosine-5'-(γ-thio)-triphosphate (ATPγS) at 3.3 Å and a medium-resolution structure of a RPG-bound mini SUR1 protein in which the N terminus of the inward-rectifying potassium channel 6.1 (Kir6.1) is fused to the ABC transporter module of the sulfonylurea receptor 1 (SUR1). These structures reveal the binding site of RPG in the SUR1 subunit. Furthermore, the high-resolution structure reveals the complex architecture of the ATP binding site, which is formed by both Kir6.2 and SUR1 subunits, and the domain-domain interaction interfaces. | |||||||||||||||
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_9787.map.gz | 8.1 MB | EMDB map data format | |
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Header (meta data) | emd-9787-v30.xml emd-9787.xml | 17.2 KB 17.2 KB | Display Display | EMDB header |
Images | emd_9787.png | 97.4 KB | ||
Others | emd_9787_additional.map.gz | 74.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9787 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9787 | HTTPS FTP |
-Validation report
Summary document | emd_9787_validation.pdf.gz | 372.3 KB | Display | EMDB validaton report |
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Full document | emd_9787_full_validation.pdf.gz | 371.8 KB | Display | |
Data in XML | emd_9787_validation.xml.gz | 6.4 KB | Display | |
Data in CIF | emd_9787_validation.cif.gz | 7.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9787 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9787 | HTTPS FTP |
-Related structure data
Related structure data | 6jb1MC 9788C 9789C 6jb3C 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_9787.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | the sharpened map from cisTEM | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.324 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: A further sharpened map by a bfactor -100
File | emd_9787_additional.map | ||||||||||||
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Annotation | A further sharpened map by a bfactor -100 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : KATP
Entire | Name: KATP |
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Components |
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-Supramolecule #1: KATP
Supramolecule | Name: KATP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: ATP-sensitive inward rectifier potassium channel 11
Macromolecule | Name: ATP-sensitive inward rectifier potassium channel 11 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 43.615734 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MLSRKGIIPE EYVLTRLAED PAEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMV WWLIAFAHGD LAPGEGTNVP CVTSIHSFSS AFLFSIEVQV TIGFGGRMVT EECPLAILIL IVQNIVGLMI N AIMLGCIF ...String: MLSRKGIIPE EYVLTRLAED PAEPRYRTRE RRARFVSKKG NCNVAHKNIR EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMV WWLIAFAHGD LAPGEGTNVP CVTSIHSFSS AFLFSIEVQV TIGFGGRMVT EECPLAILIL IVQNIVGLMI N AIMLGCIF MKTAQAHRRA ETLIFSKHAV ITLRHGRLCF MLRVGDLRKS MIISATIHMQ VVRKTTSPEG EVVPLHQVDI PM ENGVGGN GIFLVAPLII YHVIDSNSPL YDLAPSDLHH HQDLEIIVIL EGVVETTGIT TQARTSYLAD EILWGQRFVP IVA EEDGRY SVDYSKFGNT IKVPTPLCTA RQLDEDRSLL DALTLASSRG PLRKRSVAVA KAKPKFSISP DSLS |
-Macromolecule #2: ATP-binding cassette sub-family C member 8 isoform X2
Macromolecule | Name: ATP-binding cassette sub-family C member 8 isoform X2 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mesocricetus auratus (golden hamster) |
Molecular weight | Theoretical: 177.295516 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 RAIGKLPIAM RALTNYQRLC VAFDAQARKD TQSPQGARAI WRALCHAFGR RLILSSTFRI LADLLGFAGP LCI FGIVDH LGKENHVFQP KTQFLGVYFV SSQEFLGNAY VLAVLLFLAL LLQRTFLQAS YYVAIETGIN LRGAIQTKIY NKIM HLSTS NLSMGEMTAG QICNLVAIDT NQLMWFFFLC PNLWAMPVQI IVGVILLYYI LGVSALIGAA VIILLAPVQY FVATK LSQA QRSTLEHSNE 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 LSHFA ETVEGLTTIR AFRYEARFQQ KLLEYTDSNN IASLFLTAAN RWLEVRMEYI GACVVLIAAA TSISNSLHRE LSAGL VGLG LTYALMVSNY LNWMVRNLAD MEIQLGAVKR IHALLKTEAE SYEGLLAPSL IPKNWPDQGK IQIQNLSVRY DSSLKP VLK HVNALISPGQ 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 #3: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 3 / Number of copies: 36 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Macromolecule #4: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER
Macromolecule | Name: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / type: ligand / ID: 4 / Number of copies: 8 / Formula: AGS |
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Molecular weight | Theoretical: 523.247 Da |
Chemical component information | ChemComp-AGS: |
-Macromolecule #5: Digitonin
Macromolecule | Name: Digitonin / type: ligand / ID: 5 / Number of copies: 4 / Formula: AJP |
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Molecular weight | Theoretical: 1.229312 KDa |
Chemical component information | ChemComp-AJP: |
-Macromolecule #6: Repaglinide
Macromolecule | Name: Repaglinide / type: ligand / ID: 6 / Number of copies: 4 / Formula: BJX |
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Molecular weight | Theoretical: 452.586 Da |
Chemical component information | ChemComp-BJX: |
-Macromolecule #7: PHOSPHATIDYLETHANOLAMINE
Macromolecule | Name: PHOSPHATIDYLETHANOLAMINE / type: ligand / ID: 7 / Number of copies: 16 / Formula: PTY |
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Molecular weight | Theoretical: 734.039 Da |
Chemical component information | ChemComp-PTY: |
-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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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 50.0 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: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2.0) / Number images used: 277548 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |