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Yorodumi- EMDB-31958: Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-b... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31958 | |||||||||
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Title | Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-beta1 complex, apo state | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of muscle contraction / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in contraction ...regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of muscle contraction / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / NCAM1 interactions / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / neuromuscular junction development / Phase 0 - rapid depolarisation / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / response to amyloid-beta / calcium ion import across plasma membrane / voltage-gated calcium channel activity / sarcoplasmic reticulum / calcium ion transmembrane transport / modulation of chemical synaptic transmission / cellular response to amyloid-beta / calcium ion transport / amyloid-beta binding / chemical synaptic transmission / neuronal cell body / synapse / calcium ion binding / extracellular exosome / ATP binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Dong Y / Gao Y / Wang Y / Zhao Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Rep / Year: 2021 Title: Closed-state inactivation and pore-blocker modulation mechanisms of human Ca2.2. Authors: Yanli Dong / Yiwei Gao / Shuai Xu / Yuhang Wang / Zhuoya Yu / Yue Li / Bin Li / Tian Yuan / Bei Yang / Xuejun Cai Zhang / Daohua Jiang / Zhuo Huang / Yan Zhao / Abstract: N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and ...N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human Ca2.2 complex in apo, ziconotide-bound, and two Ca2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP) molecule, which is distinct from the other three VSDs of Ca2.2, as well as activated VSDs observed in previous structures of Ca channels. This structure reveals the molecular basis for the unique inactivation process of Ca2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain. | |||||||||
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_31958.map.gz | 230.3 MB | EMDB map data format | |
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Header (meta data) | emd-31958-v30.xml emd-31958.xml | 17.9 KB 17.9 KB | Display Display | EMDB header |
Images | emd_31958.png | 62.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31958 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31958 | HTTPS FTP |
-Validation report
Summary document | emd_31958_validation.pdf.gz | 447 KB | Display | EMDB validaton report |
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Full document | emd_31958_full_validation.pdf.gz | 446.6 KB | Display | |
Data in XML | emd_31958_validation.xml.gz | 7.1 KB | Display | |
Data in CIF | emd_31958_validation.cif.gz | 8.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31958 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31958 | HTTPS FTP |
-Related structure data
Related structure data | 7vfsMC 7vfuC 7vfvC 7vfwC 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_31958.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.04 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 : CaV2.2-alpha2delta1-beta1 complex
Entire | Name: CaV2.2-alpha2delta1-beta1 complex |
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Components |
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-Supramolecule #1: CaV2.2-alpha2delta1-beta1 complex
Supramolecule | Name: CaV2.2-alpha2delta1-beta1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Voltage-dependent N-type calcium channel subunit alpha-1B
Macromolecule | Name: Voltage-dependent N-type calcium channel subunit alpha-1B type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 262.831781 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVRFGDELGG RYGGPGGGER ARGGGAGGAG GPGPGGLQPG QRVLYKQSIA QRARTMALYN PIPVKQNCFT VNRSLFVFSE DNVVRKYAK RITEWPPFEY MILATIIANC IVLALEQHLP DGDKTPMSER LDDTEPYFIG IFCFEAGIKI IALGFVFHKG S YLRNGWNV ...String: MVRFGDELGG RYGGPGGGER ARGGGAGGAG GPGPGGLQPG QRVLYKQSIA QRARTMALYN PIPVKQNCFT VNRSLFVFSE DNVVRKYAK RITEWPPFEY MILATIIANC IVLALEQHLP DGDKTPMSER LDDTEPYFIG IFCFEAGIKI IALGFVFHKG S YLRNGWNV MDFVVVLTGI LATAGTDFDL RTLRAVRVLR PLKLVSGIPS LQVVLKSIMK AMVPLLQIGL LLFFAILMFA II GLEFYMG KFHKACFPNS TDAEPVGDFP CGKEAPARLC EGDTECREYW PGPNFGITNF DNILFAILTV FQCITMEGWT DIL YNTNDA AGNTWNWLYF IPLIIIGSFF MLNLVLGVLS GEFAKERERV ENRRAFLKLR RQQQIERELN GYLEWIFKAE EVML AEEDR NAEEKSPLDV LKRAATKKSR NDLIHAEEGE DRFADLCAVG SPFARASLKS GKTESSSYFR RKEKMFRFFI RRMVK AQSF YWVVLCVVAL NTLCVAMVHY NQPRRLTTTL YFAEFVFLGL FLTEMSLKMY GLGPRSYFRS SFNCFDFGVI VGSVFE VVW AAIKPGSSFG ISVLRALRLL RIFKVTKYWS SLRNLVVSLL NSMKSIISLL FLLFLFIVVF ALLGMQLFGG QFNFQDE TP TTNFDTFPAA ILTVFQILTG EDWNAVMYHG IESQGGVSKG MFSSFYFIVL TLFGNYTLLN VFLAIAVDNL ANAQELTK D EEEMEEAANQ KLALQKAKEV AEVSPMSAAN ISIAARQQNS AKARSVWEQR ASQLRLQNLR ASCEALYSEM DPEERLRFA TTRHLRPDMK THLDRPLVVE LGRDGARGPV GGKARPEAAE APEGVDPPRR HHRHRDKDKT PAAGDQDRAE APKAESGEPG AREERPRPH RSHSKEAAGP PEARSERGRG PGPEGGRRHH RRGSPEEAAE REPRRHRAHR HQDPSKECAG AKGERRARHR G GPRAGPRE AESGEEPARR HRARHKAQPA HEAVEKETTE KEATEKEAEI VEADKEKELR NHQPREPHCD LETSGTVTVG PM HTLPSTC LQKVEEQPED ADNQRNVTRM GSQPPDPNTI VHIPVMLTGP LGEATVVPSG NVDLESQAEG KKEVEADDVM RSG PRPIVP YSSMFCLSPT NLLRRFCHYI VTMRYFEVVI LVVIALSSIA LAAEDPVRTD SPRNNALKYL DYIFTGVFTF EMVI KMIDL GLLLHPGAYF RDLWNILDFI VVSGALVAFA FSGSKGKDIN TIKSLRVLRV LRPLKTIKRL PKLKAVFDCV VNSLK NVLN ILIVYMLFMF IFAVIAVQLF KGKFFYCTDE SKELERDCRG QYLDYEKEEV EAQPRQWKKY DFHYDNVLWA LLTLFT VST GEGWPMVLKH SVDATYEEQG PSPGYRMELS IFYVVYFVVF PFFFVNIFVA LIIITFQEQG DKVMSECSLE KNERACI DF AISAKPLTRY MPQNRQSFQY KTWTFVVSPP FEYFIMAMIA LNTVVLMMKF YDAPYEYELM LKCLNIVFTS MFSMECVL K IIAFGVLNYF RDAWNVFDFV TVLGSITDIL VTEIAETNNF INLSFLRLFR AARLIKLLRQ GYTIRILLWT FVQSFKALP YVCLLIAMLF FIYAIIGMQV FGNIALDDDT SINRHNNFRT FLQALMLLFR SATGEAWHEI MLSCLSNQAC DEQANATECG SDFAYFYFV SFIFLCSFLM LNLFVAVIMD NFEYLTRDSS ILGPHHLDEF IRVWAEYDPA ACGRISYNDM FEMLKHMSPP L GLGKKCPA RVAYKRLVRM NMPISNEDMT VHFTSTLMAL IRTALEIKLA PAGTKQHQCD AELRKEISVV WANLPQKTLD LL VPPHKPD EMTVGKVYAA LMIFDFYKQN KTTRDQMQQA PGGLSQMGPV SLFHPLKATL EQTQPAVLRG ARVFLRQKSS TSL SNGGAI QNQESGIKES VSWGTQRTQD APHEARPPLE RGHSTEIPVG RSGALAVDVQ MQSITRRGPD GEPQPGLESQ GRAA SMPRL AAETQPVTDA SPMKRSISTL AQRPRGTHLC STTPDRPPPS QASSHHHHHR CHRRRDRKQR SLEKGPSLSA DMDGA PSSA VGPGLPPGEG PTGCRRERER RQERGRSQER RQPSSSSSEK QRFYSCDRFG GREPPKPKPS LSSHPTSPTA GQEPGP HPQ GSGSVNGSPL LSTSGASTPG RGGRRQLPQT PLTPRPSITY KTANSSPIHF AGAQTSLPAF SPGRLSRGLS EHNALLQ RD PLSQPLAPGS RIGSDPYLGQ RLDSEASVHA LPEDTLTFEE AVATNSGRSS RTSYVSSLTS QSHPLRRVPN GYHCTLGL S SGGRARHSYH HPDQDHWC |
-Macromolecule #2: Voltage-dependent calcium channel subunit alpha-2/delta-1
Macromolecule | Name: Voltage-dependent calcium channel subunit alpha-2/delta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 124.692469 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKL LSNRSKALVR LALEAEKVQA AHQWREDFAS NEVVYYNAKD DLDPEKNDSE PGSQRIKPVF IEDANFGRQI S YQHAAVHI ...String: MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKL LSNRSKALVR LALEAEKVQA AHQWREDFAS NEVVYYNAKD DLDPEKNDSE PGSQRIKPVF IEDANFGRQI S YQHAAVHI PTDIYEGSTI VLNELNWTSA LDEVFKKNRE EDPSLLWQVF GSATGLARYY PASPWVDNSR TPNKIDLYDV RR RPWYIQG AASPKDMLIL VDVSGSVSGL TLKLIRTSVS EMLETLSDDD FVNVASFNSN AQDVSCFQHL VQANVRNKKV LKD AVNNIT AKGITDYKKG FSFAFEQLLN YNVSRANCNK IIMLFTDGGE ERAQEIFNKY NKDKKVRVFT FSVGQHNYDR GPIQ WMACE NKGYYYEIPS IGAIRINTQE YLDVLGRPMV LAGDKAKQVQ WTNVYLDALE LGLVITGTLP VFNITGQFEN KTNLK NQLI LGVMGVDVSL EDIKRLTPRF TLCPNGYYFA IDPNGYVLLH PNLQPKPIGV GIPTINLRKR RPNIQNPKSQ EPVTLD FLD AELENDIKVE IRNKMIDGES GEKTFRTLVK SQDERYIDKG NRTYTWTPVN GTDYSLALVL PTYSFYYIKA KLEETIT QA RYSETLKPDN FEESGYTFIA PRDYCNDLKI SDNNTEFLLN FNEFIDRKTP NNPSCNADLI NRVLLDAGFT NELVQNYW S KQKNIKGVKA RFVVTDGGIT RVYPKEAGEN WQENPETYED SFYKRSLDND NYVFTAPYFN KSGPGAYESG IMVSKAVEI YIQGKLLKPA VVGIKIDVNS WIENFTKTSI RDPCAGPVCD CKRNSDVMDC VILDDGGFLL MANHDDYTNQ IGRFFGEIDP SLMRHLVNI SVYAFNKSYD YQSVCEPGAA PKQGAGHRSA YVPSVADILQ IGWWATAAAW SILQQFLLSL TFPRLLEAVE M EDDDFTAS LSKQSCITEQ TQYFFDNDSK SFSGVLDCGN CSRIFHGEKL MNTNLIFIMV ESKGTCPCDT RLLIQAEQTS DG PNPCDMV KQPRYRKGPD VCFDNNVLED YTDCGGVSGL NPSLWYIIGI QFLLLWLVSG STHRLL |
-Macromolecule #3: Voltage-dependent L-type calcium channel subunit beta-1
Macromolecule | Name: Voltage-dependent L-type calcium channel subunit beta-1 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 65.799594 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MVQKTSMSRG PYPPSQEIPM EVFDPSPQGK YSKRKGRFKR SDGSTSSDTT SNSFVRQGSA ESYTSRPSDS DVSLEEDREA LRKEAERQA LAQLEKAKTK PVAFAVRTNV GYNPSPGDEV PVQGVAITFE PKDFLHIKEK YNNDWWIGRL VKEGCEVGFI P SPVKLDSL ...String: MVQKTSMSRG PYPPSQEIPM EVFDPSPQGK YSKRKGRFKR SDGSTSSDTT SNSFVRQGSA ESYTSRPSDS DVSLEEDREA LRKEAERQA LAQLEKAKTK PVAFAVRTNV GYNPSPGDEV PVQGVAITFE PKDFLHIKEK YNNDWWIGRL VKEGCEVGFI P SPVKLDSL RLLQEQKLRQ NRLGSSKSGD NSSSSLGDVV TGTRRPTPPA SAKQKQKSTE HVPPYDVVPS MRPIILVGPS LK GYEVTDM MQKALFDFLK HRFDGRISIT RVTADISLAK RSVLNNPSKH IIIERSNTRS SLAEVQSEIE RIFELARTLQ LVA LDADTI NHPAQLSKTS LAPIIVYIKI TSPKVLQRLI KSRGKSQSKH LNVQIAASEK LAQCPPEMFD IILDENQLED ACEH LAEYL EAYWKATHPP SSTPPNPLLN RTMATAALAA SPAPVSNLQG PYLASGDQPL ERATGEHASM HEYPGELGQP PGLYP SSHP PGRAGTLRAL SRQDTFDADT PGSRNSAYTE LGDSCVDMET DPSEGPGLGD PAGGGTPPAR QGSWEDEEED YEEELT DNR NRGRNKARYC AEGGGPVLGR NKNELEGWGR GVYIR |
-Macromolecule #6: HEXADECANE
Macromolecule | Name: HEXADECANE / type: ligand / ID: 6 / Number of copies: 18 / Formula: R16 |
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Molecular weight | Theoretical: 226.441 Da |
Chemical component information | ChemComp-R16: |
-Macromolecule #7: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 7 / Number of copies: 3 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-Macromolecule #8: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...
Macromolecule | Name: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate type: ligand / ID: 8 / Number of copies: 1 / Formula: PT5 |
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Molecular weight | Theoretical: 1.047088 KDa |
-Macromolecule #9: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 9 / Number of copies: 2 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 8 / 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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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 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 9.6 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 |