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- EMDB-18198: Helical reconstruction of the relaxed thick filament from FIB mil... -
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Title | Helical reconstruction of the relaxed thick filament from FIB milled left ventricular mouse myofibrils | ||||||||||||||||||
![]() | Helical reconstruction of the relaxed thick filament from FIB-milled mouse left ventricular myofibrils | ||||||||||||||||||
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![]() | Mammalian / Muscle / Thick filament / Cardiac / MOTOR PROTEIN | ||||||||||||||||||
Function / homology | ![]() forward locomotion / heart growth / striated muscle cell development / regulation of relaxation of cardiac muscle / muscle cell fate specification / Striated Muscle Contraction / regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / contractile muscle fiber / cardiac myofibril ...forward locomotion / heart growth / striated muscle cell development / regulation of relaxation of cardiac muscle / muscle cell fate specification / Striated Muscle Contraction / regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / contractile muscle fiber / cardiac myofibril / regulation of striated muscle contraction / cardiac myofibril assembly / muscle myosin complex / muscle filament sliding / ventricular system development / detection of muscle stretch / transition between fast and slow fiber / regulation of the force of heart contraction / muscle cell development / myosin filament / cardiac muscle tissue morphogenesis / adult heart development / cardiac muscle hypertrophy in response to stress / cardiac muscle tissue development / M band / I band / myosin complex / A band / ventricular cardiac muscle tissue morphogenesis / structural constituent of muscle / ankyrin binding / intracellular non-membrane-bounded organelle / myosin II complex / microfilament motor activity / myofibril / sarcomere organization / heart contraction / cytoskeletal motor activity / positive regulation of the force of heart contraction / skeletal muscle contraction / actin monomer binding / somitogenesis / striated muscle contraction / heart morphogenesis / cardiac muscle contraction / stress fiber / ATP metabolic process / regulation of heart rate / sarcomere / post-embryonic development / muscle contraction / structural constituent of cytoskeleton / negative regulation of cell growth / Z disc / actin filament binding / actin cytoskeleton / heart development / protein tyrosine kinase activity / in utero embryonic development / cytoskeleton / non-specific serine/threonine protein kinase / calmodulin binding / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / calcium ion binding / protein-containing complex binding / ATP hydrolysis activity / ATP binding / identical protein binding / nucleus / metal ion binding / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | subtomogram averaging / cryo EM / Resolution: 18.0 Å | ||||||||||||||||||
![]() | Tamborrini D / Raunser S | ||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structure of the native myosin filament in the relaxed cardiac sarcomere. Authors: Davide Tamborrini / Zhexin Wang / Thorsten Wagner / Sebastian Tacke / Markus Stabrin / Michael Grange / Ay Lin Kho / Martin Rees / Pauline Bennett / Mathias Gautel / Stefan Raunser / ![]() ![]() Abstract: The thick filament is a key component of sarcomeres, the basic units of striated muscle. Alterations in thick filament proteins are associated with familial hypertrophic cardiomyopathy and other ...The thick filament is a key component of sarcomeres, the basic units of striated muscle. Alterations in thick filament proteins are associated with familial hypertrophic cardiomyopathy and other heart and muscle diseases. Despite the central importance of the thick filament, its molecular organization remains unclear. Here we present the molecular architecture of native cardiac sarcomeres in the relaxed state, determined by cryo-electron tomography. Our reconstruction of the thick filament reveals the three-dimensional organization of myosin, titin and myosin-binding protein C (MyBP-C). The arrangement of myosin molecules is dependent on their position along the filament, suggesting specialized capacities in terms of strain susceptibility and force generation. Three pairs of titin-α and titin-β chains run axially along the filament, intertwining with myosin tails and probably orchestrating the length-dependent activation of the sarcomere. Notably, whereas the three titin-α chains run along the entire length of the thick filament, titin-β chains do not. The structure also demonstrates that MyBP-C bridges thin and thick filaments, with its carboxy-terminal region binding to the myosin tails and directly stabilizing the OFF state of the myosin heads in an unforeseen manner. These results provide a foundation for future research investigating muscle disorders involving sarcomeric components. | ||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 1.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.5 KB 19.5 KB | Display Display | ![]() |
Images | ![]() | 43 KB | ||
Filedesc metadata | ![]() | 8.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 355.7 KB | Display | ![]() |
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Full document | ![]() | 355.3 KB | Display | |
Data in XML | ![]() | 7.2 KB | Display | |
Data in CIF | ![]() | 8.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8q6tMC ![]() 8q4gC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 | Helical reconstruction of the relaxed thick filament from FIB-milled mouse left ventricular myofibrils | ||||||||||||||||||||
Voxel size | X=Y=Z: 5.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Relaxed thick filament; A-band region; C-type super-repeat
Entire | Name: Relaxed thick filament; A-band region; C-type super-repeat |
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Components |
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-Supramolecule #1: Relaxed thick filament; A-band region; C-type super-repeat
Supramolecule | Name: Relaxed thick filament; A-band region; C-type super-repeat type: cell / ID: 1 / Parent: 0 / Macromolecule list: #1-#3, #5, #4 Details: Single asymmetrical unit from the relaxed thick filament obtained from FIB milled left ventricular mouse myofibrils |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Myosin-7
Macromolecule | Name: Myosin-7 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 223.226531 KDa |
Sequence | String: MADAEMAAFG AAAPFLRKSE KERLEAQTRP FDLKKDVFVP DDKEEFVKAK IVSREGGKVT AETENGKTVT VKEDQVMQQN PPKFDKIED MAMLTFLHEP AVLYNLKERY ASWMIYTYSG LFCVTVNPYK WLPVYNAEVV AAYRGKKRSE APPHIFSISD N AYQYMLTD ...String: MADAEMAAFG AAAPFLRKSE KERLEAQTRP FDLKKDVFVP DDKEEFVKAK IVSREGGKVT AETENGKTVT VKEDQVMQQN PPKFDKIED MAMLTFLHEP AVLYNLKERY ASWMIYTYSG LFCVTVNPYK WLPVYNAEVV AAYRGKKRSE APPHIFSISD N AYQYMLTD RENQSILITG ESGAGKTVNT KRVIQYFAVI AAIGDRSKKD QTPGKGTLED QIIQANPALE AFGNAKTVRN DN SSRFGKF IRIHFGATGK LASADIETYL LEKSRVIFQL KAERDYHIFY QILSNKKPEL LDMLLITNNP YDYAFISQGE TTV ASIDDS EELMATDSAF DVLGFTPEEK NSIYKLTGAI MHFGNMKFKQ KQREEQAEPD GTEEADKSAY LMGLNSADLL KGLC HPRVK VGNEYVTKGQ NVQQVSYAIG ALAKSVYEKM FNWMVTRINA TLETKQPRQY FIGVLDIAGF EIFDFNSFEQ LCINF TNEK LQQFFNHHMF VLEQEEYKKE GIEWTFIDFG MDLQACIDLI EKPMGIMSIL EEECMFPKAT DMTFKAKLYD NHLGKS NNF QKPRNVKGKQ EAHFSLVHYA GTVDYNILGW LQKNKDPLNE TVVGLYQKSS LKLLSNLFAN YAGADAPADK GKGKAKK GS SFQTVSALHR ENLNKLMTNL RSTHPHFVRC IIPNETKSPG VMDNPLVMHQ LRCNGVLEGI RICRKGFPNR ILYGDFRQ R YRILNPAAIP EGQFIDSRKG AEKLLGSLDI DHNQYKFGHT KVFFKAGLLG LLEEMRDERL SRIITRIQAQ SRGVLSRME FKKLLERRDS LLIIQWNIRA FMGVKNWPWM KLYFKIKPLL KSAETEKEMA TMKEEFGRVK DALEKSEARR KELEEKMVSL LQEKNDLQL QVQAEQDNLA DAEERCDQLI KNKIQLEAKV KEMTERLEDE EEMNAELTAK KRKLEDECSE LKRDIDDLEL T LAKVEKEK HATENKVKNL TEEMAGLDEI IVKLTKEKKA LQEAHQQALD DLQAEEDKVN TLTKAKVKLE QQVDDLEGSL EQ EKKVRMD LERAKRKLEG DLKLTQESIM DLENDKQQLD ERLKKKDFEL NALNARIEDE QALGSQLQKK LKELQARIEE LEE ELEAER TARAKVEKLR SDLSRELEEI SERLEEAGGA TSVQIEMNKK REAEFQKMRR DLEEATLQHE ATAAALRKKH ADSV AELGE QIDNLQRVKQ KLEKEKSEFK LELDDVTSNM EQIIKAKANL EKMCRTLEDQ MNEHRSKAEE TQRSVNDLTS QRAKL QTEN GELSRQLDEK EALISQLTRG KLTYTQQLED LKRQLEEEVK AKNALAHALQ SARHDCDLLR EQYEEETEAK AELQRV LSK ANSEVAQWRT KYETDAIQRT EELEEAKKKL AQRLQDAEEA VEAVNAKCSS LEKTKHRLQN EIEDLMVDVE RSNAAAA AL DKKQRNFDKI LAEWKQKYEE SQSELESSQK EARSLSTELF KLKNAYEESL EHLETFKREN KNLQEEISDL TEQLGSTG K SIHELEKIRK QLEAEKLELQ SALEEAEASL EHEEGKILRA QLEFNQIKAE IERKLAEKDE EMEQAKRNHL RMVDSLQTS LDAETRSRNE ALRVKKKMEG DLNEMEIQLS HANRMAAEAQ KQVKSLQSLL KDTQIQLDDA VRANDDLKEN IAIVERRNNL LQAELEELR AVVEQTERSR KLAEQELIET SERVQLLHSQ NTSLINQKKK MDADLSQLQT EVEEAVQECR NAEEKAKKAI T DAAMMAEE LKKEQDTSAH LERMKKNMEQ TIKDLQHRLD EAEQIALKGG KKQLQKLEAR VRELENELEA EQKRNAESVK GM RKSERRI KELTYQTEED RKNLLRLQDL VDKLQLKVKA YKRQAEEAEE QANTNLSKFR KVQHELDEAE ERADIAESQV NKL RAKSRD IGAKGLNEE UniProtKB: Myosin-7 |
-Macromolecule #2: Myosin light chain 3
Macromolecule | Name: Myosin light chain 3 / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 17.243553 KDa |
Sequence | String: IEFTPEQIEE FKEAFLLFDR TPKGEMKITY GQCGDVLRAL GQNPTQAEVL RVLGKPKQEE LNSKMMDFET FLPMLQHISK NKDTGTYED FVEGLRVFDK EGNGTVMGAE LRHVLATLGE RLTEDEVEKL MAGQEDSNGC INYEAFVKHI MAS UniProtKB: Myosin light chain 3 |
-Macromolecule #3: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
Macromolecule | Name: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform type: protein_or_peptide / ID: 3 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 18.259512 KDa |
Sequence | String: KKRIEGGSSN VFSMFEQTQI QEFKEAFTIM DQNRDGFIDK NDLRDTFAAL GRVNVKNEEI DEMIKEAPGP INFTVFLTMF GEKLKGADP EETILNAFKV FDPEGKGSLK ADYVREMLTT QAERFSKEEI DQMFAAFPPD VTGNLDYKNL VHIITHGEEK D UniProtKB: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform |
-Macromolecule #4: Myosin binding protein C, cardiac
Macromolecule | Name: Myosin binding protein C, cardiac / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 44.777125 KDa |
Sequence | String: PIGPPGEPTH LAVEDVSDTT VSLKWRPPER VGAGGLDGYS VEYCQEGCSE WTPALQGLTE RTSMLVKDLP TGARLLFRVR AHNVAGPGG PIVTKEPVTV QEILQRPRLQ LPRHLRQTIQ KKVGEPVNLL IPFQGKPRPQ VTWTKEGQPL AGEEVSIRNS P TDTILFIR ...String: PIGPPGEPTH LAVEDVSDTT VSLKWRPPER VGAGGLDGYS VEYCQEGCSE WTPALQGLTE RTSMLVKDLP TGARLLFRVR AHNVAGPGG PIVTKEPVTV QEILQRPRLQ LPRHLRQTIQ KKVGEPVNLL IPFQGKPRPQ VTWTKEGQPL AGEEVSIRNS P TDTILFIR AARRTHSGTY QVTVRIENME DKATLILQIV DKPSPPQDIR IVETWGFNVA LEWKPPQDDG NTEIWGYTVQ KA DKKTMEW FTVLEHYRRT HCVVSELIIG NGYYFRVFSH NMVGSSDKAA ATKEPVFIPR PGITYEPPKY KALDFSEAPS FTQ PLANRS IIAGYNAILC CAVRGSPKPK ISWFKNGLDL GEDARFRMFC KQGVLTLEIR KPCPYDGGVY VCRATNLQGE AQCE UniProtKB: Myosin binding protein C, cardiac |
-Macromolecule #5: Titin
Macromolecule | Name: Titin / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 118.76632 KDa |
Sequence | String: DPCDPPGRPE AIVITRNSVT LKWKKPVYDG GSKITGYIVE KKDLPDGRWM KASFTNVVET EFTVTGLVED QRYEFRVIAR NAADNFSEP SESSGAITAR DEIDAPNASL DPKYRDVIIV HAGETFVLEA DIRGKPIPDI IWSKDGNELE ETAARMEIKS T LQKTTLIV ...String: DPCDPPGRPE AIVITRNSVT LKWKKPVYDG GSKITGYIVE KKDLPDGRWM KASFTNVVET EFTVTGLVED QRYEFRVIAR NAADNFSEP SESSGAITAR DEIDAPNASL DPKYRDVIIV HAGETFVLEA DIRGKPIPDI IWSKDGNELE ETAARMEIKS T LQKTTLIV KDCIRTDGGQ YTLKLSNVGG TKTIPITVKV LDRPGPPEGP LKVTGVTAEK CYLAWNPPLQ DGGASISHYI IE KRETSRL SWTQVSNEVQ ALNYKVTKLL PGNEYIFRVM AVNKYGIGEA LESEPVIACN PYKRPGPPST PEASAITKDS MVL TWTRPV DDGGAEIEGY ILEKRDKEGI RWTKCNKKTL TDLRFRVTGL TEGHSYEFRV AAENAAGVGE PSEPSVFYRA CDAL YPPGP PSNPKVTDTS RSSVSLAWNK PIYDGGAPVR GYVIELKKAA ADEWTTCTPP SGLQGKQFTV TKLKENTEYN FRICA FNTE GVGEPATIPG SVVAQERMEA PEIELDADLR KVVTLRASAT LRLFVTIKGR PEPEVKWEKA EGILTERAQI EVTSSY TML VIDNVTRFDS GRYNLTLENN SGSKTAFVNV RVLDSPSAPV NLTIREVKKD SVTLSWEPPL IDGGAKITNY IVEKRET TR KAYATITNNC TKNTFKIENL QEGCSYYFRV LASNEYGIGL PAETAEPVKV SEPPLPPGRV TLVDVTRNTA TIKWEKPE S DGGSKITGYV VEMQTKGSEK WSACTQVKTL ETTISGLTAG EEYVFRVAAV NEKGRSDPRQ LGVPVIAKDI EIKPSVELP FNTFNVKAND QLKIDIPFKG RPQATVAWKK DGQVLRETTR VNVASSKTVT TLSIKEASRE DVGTYELCVS NTAGSITVPI TVIVLDRPG PPGPIRIDEV SCDNVSISWN PPEYDGGCQI SNYIVEKRET TSTTWQVVSQ AVARTSIKIV RLTTGSEYQF R VCAENRYG KSSYSESSAV VAEYPFSPPG PPGTPKVVHA TKSTMVVSWQ VPVNDGGSQV IGYHLEYKER SSILWSKANK VL IADTQMK VSGLDEGLMY EYRVYAENIA GIGKCSKACE PV UniProtKB: Titin |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | subtomogram averaging |
Aggregation state | cell |
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Sample preparation
Buffer | pH: 7.1 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 3.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 6.0 µm / Nominal defocus min: 3.0 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Helical parameters - Δz: 430.0 Å Applied symmetry - Helical parameters - Δ&Phi: 0 ° Applied symmetry - Helical parameters - Axial symmetry: C3 (3 fold cyclic) Resolution.type: BY AUTHOR / Resolution: 18.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION Details: Helical reconstruction containing 4.5x repeats extrapolated from a 3x repeat reconstruction (EMD-18146) Number subtomograms used: 1589 |
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Extraction | Number tomograms: 89 / Number images used: 67492 |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION |
-Atomic model buiding 1
Initial model | (Chain: AlphaFold, SwissModel) |
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Output model | ![]() PDB-8q6t: |