[English] 日本語
![](img/lk-miru.gif)
- EMDB-27908: Human L-type voltage-gated calcium channel Cav1.3 treated with 1.... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human L-type voltage-gated calcium channel Cav1.3 treated with 1.4 mM Sofosbuvir at 3.3 Angstrom resolution | |||||||||
![]() | calcium channel | |||||||||
![]() |
| |||||||||
Function / homology | ![]() voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential ...voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / positive regulation of adenylate cyclase activity / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of calcium ion transport / cardiac muscle cell action potential involved in contraction / regulation of potassium ion transmembrane transport / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion import / Sensory processing of sound by inner hair cells of the cochlea / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / ankyrin binding / neuromuscular junction development / calcium ion import across plasma membrane / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / alpha-actinin binding / regulation of calcium ion transport / calcium channel regulator activity / voltage-gated calcium channel activity / sarcoplasmic reticulum / protein localization to plasma membrane / Regulation of insulin secretion / calcium ion transmembrane transport / sensory perception of sound / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / calcium channel activity / Z disc / Adrenaline,noradrenaline inhibits insulin secretion / cellular response to amyloid-beta / calcium ion transport / T cell receptor signaling pathway / chemical synaptic transmission / synapse / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Gao S / Yao X / Yan N | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Structural basis for the severe adverse interaction of sofosbuvir and amiodarone on L-type Ca channels. Authors: Xia Yao / Shuai Gao / Jixin Wang / Zhangqiang Li / Jian Huang / Yan Wang / Zhifei Wang / Jiaofeng Chen / Xiao Fan / Weipeng Wang / Xueqin Jin / Xiaojing Pan / Yong Yu / Armando Lagrutta / Nieng Yan / ![]() ![]() Abstract: Drug-drug interaction of the antiviral sofosbuvir and the antiarrhythmics amiodarone has been reported to cause fatal heartbeat slowing. Sofosbuvir and its analog, MNI-1, were reported to potentiate ...Drug-drug interaction of the antiviral sofosbuvir and the antiarrhythmics amiodarone has been reported to cause fatal heartbeat slowing. Sofosbuvir and its analog, MNI-1, were reported to potentiate the inhibition of cardiomyocyte calcium handling by amiodarone, which functions as a multi-channel antagonist, and implicate its inhibitory effect on L-type Ca channels, but the molecular mechanism has remained unclear. Here we present systematic cryo-EM structural analysis of Ca1.1 and Ca1.3 treated with amiodarone or sofosbuvir alone, or sofosbuvir/MNI-1 combined with amiodarone. Whereas amiodarone alone occupies the dihydropyridine binding site, sofosbuvir is not found in the channel when applied on its own. In the presence of amiodarone, sofosbuvir/MNI-1 is anchored in the central cavity of the pore domain through specific interaction with amiodarone and directly obstructs the ion permeation path. Our study reveals the molecular basis for the physical, pharmacodynamic interaction of two drugs on the scaffold of Ca channels. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 78.4 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 19.9 KB 19.9 KB | Display Display | ![]() |
Images | ![]() | 107 KB | ||
Others | ![]() ![]() | 65.4 MB 65.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e5aMC ![]() 8e56C ![]() 8e57C ![]() 8e58C ![]() 8e59C ![]() 8e5bC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | calcium channel | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.114 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Half Map 1
File | emd_27908_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half Map 2
File | emd_27908_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half Map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Cav1.3
Entire | Name: Cav1.3 |
---|---|
Components |
|
-Supramolecule #1: Cav1.3
Supramolecule | Name: Cav1.3 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3 |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Voltage-dependent L-type calcium channel subunit alpha-1D
Macromolecule | Name: Voltage-dependent L-type calcium channel subunit alpha-1D type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 245.417734 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD IFILLAIFAN CVALAIYIPF PEDDSNSTNH N LEKVEYAF ...String: MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD IFILLAIFAN CVALAIYIPF PEDDSNSTNH N LEKVEYAF LIIFTVETFL KIIAYGLLLH PNAYVRNGWN LLDFVIVIVG LFSVILEQLT KETEGGNHSS GKSGGFDVKA LR AFRVLRP LRLVSGVPSL QVVLNSIIKA MVPLLHIALL VLFVIIIYAI IGLELFIGKM HKTCFFADSD IVAEEDPAPC AFS GNGRQC TANGTECRSG WVGPNGGITN FDNFAFAMLT VFQCITMEGW TDVLYWMNDA MGFELPWVYF VSLVIFGSFF VLNL VLGVL SGEFSKEREK AKARGDFQKL REKQQLEEDL KGYLDWITQA EDIDPENEEE GGEEGKRNTS MPTSETESVN TENVS GEGE NRGCCGSLCQ AISKSKLSRR WRRWNRFNRR RCRAAVKSVT FYWLVIVLVF LNTLTISSEH YNQPDWLTQI QDIANK VLL ALFTCEMLVK MYSLGLQAYF VSLFNRFDCF VVCGGITETI LVELEIMSPL GISVFRCVRL LRIFKVTRHW TSLSNLV AS LLNSMKSIAS LLLLLFLFII IFSLLGMQLF GGKFNFDETQ TKRSTFDNFP QALLTVFQIL TGEDWNAVMY DGIMAYGG P SSSGMIVCIY FIILFICGNY ILLNVFLAIA VDNLADAESL NTAQKEEAEE KERKKIARKE SLENKKNNKP EVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFT NLILVFIMLS SAALAAEDPI RSHSFRNTIL GYFDYAFTAI FTVEILLKMT TFGAFLHKGA FCRNYFNLLD M LVVGVSLV SFGIQSSAIS VVKILRVLRV LRPLRAINRA KGLKHVVQCV FVAIRTIGNI MIVTTLLQFM FACIGVQLFK GK FYRCTDE AKSNPEECRG LFILYKDGDV DSPVVRERIW QNSDFNFDNV LSAMMALFTV STFEGWPALL YKAIDSNGEN IGP IYNHRV EISIFFIIYI IIVAFFMMNI FVGFVIVTFQ EQGEKEYKNC ELDKNQRQCV EYALKARPLR RYIPKNPYQY KFWY VVNSS PFEYMMFVLI MLNTLCLAMQ HYEQSKMFND AMDILNMVFT GVFTVEMVLK VIAFKPKGYF SDAWNTFDSL IVIGS IIDV ALSEADPTES ENVPVPTATP GNSEESNRIS ITFFRLFRVM RLVKLLSRGE GIRTLLWTFI KSFQALPYVA LLIAML FFI YAVIGMQMFG KVAMRDNNQI NRNNNFQTFP QAVLLLFRCA TGEAWQEIML ACLPGKLCDP ESDYNPGEEY TCGSNFA IV YFISFYMLCA FLIINLFVAV IMDNFDYLTR DWSILGPHHL DEFKRIWSEY DPEAKGRIKH LDVVTLLRRI QPPLGFGK L CPHRVACKRL VAMNMPLNSD GTVMFNATLF ALVRTALKIK TEGNLEQANE ELRAVIKKIW KKTSMKLLDQ VVPPAGDDE VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK RNGALLGNH VNHVNSDRRD SLQQTNTTHR PLHVQRPSIP PASDTEKPLF PPAGNSVCHN HHNHNSIGKQ VPTSTNANLN N ANMSKAAH GKRPSIGNLE HVSENGHHSS HKHDREPQRR SSVKRTRYYE TYIRSDSGDE QLPTICREDP EIHGYFRDPH CL GEQEYFS SEECYEDDSS PTWSRQNYGY YSRYPGRNID SERPRGYHHP QGFLEDDDSP VCYDSRRSPR RRLLPPTPAS HRR SSFNFE CLRRQSSQEE VPSSPIFPHR TALPLHLMQQ QIMAVAGLDS SKAQKYSPSH STRSWATPPA TPPYRDWTPC YTPL IQVEQ SEALDQVNGS LPSLHRSSWY TDEPDISYRT FTPASLTVPS SFRNKNSDKQ RSADSLVEAV LISEGLGRYA RDPKF VSAT KHEIADACDL TIDEMESAAS TLLNGNVRPR ANGDVGPLSH RQDYELQDFG PGYSDEEPDP GRDEEDLADE MICITT L |
-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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 124.692469 KDa |
Recombinant expression | Organism: ![]() |
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-3
Macromolecule | Name: Voltage-dependent L-type calcium channel subunit beta-3 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 54.607852 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MYDDSYVPGF EDSEAGSADS YTSRPSLDSD VSLEEDRESA RREVESQAQQ QLERAKHKPV AFAVRTNVSY CGVLDEECPV QGSGVNFEA KDFLHIKEKY SNDWWIGRLV KEGGDIAFIP SPQRLESIRL KQEQKARRSG NPSSLSDIGN RRSPPPSLAK Q KQKQAEHV ...String: MYDDSYVPGF EDSEAGSADS YTSRPSLDSD VSLEEDRESA RREVESQAQQ QLERAKHKPV AFAVRTNVSY CGVLDEECPV QGSGVNFEA KDFLHIKEKY SNDWWIGRLV KEGGDIAFIP SPQRLESIRL KQEQKARRSG NPSSLSDIGN RRSPPPSLAK Q KQKQAEHV PPYDVVPSMR PVVLVGPSLK GYEVTDMMQK ALFDFLKHRF DGRISITRVT ADLSLAKRSV LNNPGKRTII ER SSARSSI AEVQSEIERI FELAKSLQLV VLDADTINHP AQLAKTSLAP IIVFVKVSSP KVLQRLIRSR GKSQMKHLTV QMM AYDKLV QCPPESFDVI LDENQLEDAC EHLAEYLEVY WRATHHPAPG PGLLGPPSAI PGLQNQQLLG ERGEEHSPLE RDSL MPSDE ASESSRQAWT GSSQRSSRHL EEDYADAYQD LYQPHRQHTS GLPSANGHDP QDRLLAQDSE HNHSDRNWQR NRPWP KDSY |
-Macromolecule #7: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 7 / Number of copies: 2 / Formula: CA |
---|---|
Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 2 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 1.9000000000000001 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 73092 |
---|---|
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |