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Yorodumi- EMDB-15353: structure of the human beta-cardiac myosin folded-back off state -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-15353 | ||||||||||||
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Title | structure of the human beta-cardiac myosin folded-back off state | ||||||||||||
Map data | density map of the IHMof b-cardiac myosin | ||||||||||||
Sample |
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Keywords | Cardiac Myosin / Myosin / Human / folded-back off state / CONTRACTILE PROTEIN | ||||||||||||
Function / homology | Function and homology information myosin II heavy chain binding / muscle cell fate specification / regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / cardiac myofibril / regulation of striated muscle contraction / cardiac myofibril assembly / muscle myosin complex / muscle filament sliding / transition between fast and slow fiber ...myosin II heavy chain binding / muscle cell fate specification / regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / cardiac myofibril / regulation of striated muscle contraction / cardiac myofibril assembly / muscle myosin complex / muscle filament sliding / transition between fast and slow fiber / regulation of the force of heart contraction / myosin filament / adult heart development / cardiac muscle hypertrophy in response to stress / positive regulation of ATP-dependent activity / Striated Muscle Contraction / I band / myosin complex / A band / ventricular cardiac muscle tissue morphogenesis / structural constituent of muscle / myosin II complex / microfilament motor activity / myofibril / sarcomere organization / heart contraction / myosin heavy chain binding / positive regulation of the force of heart contraction / skeletal muscle contraction / actin monomer binding / striated muscle contraction / cardiac muscle contraction / stress fiber / ATP metabolic process / regulation of heart rate / sarcomere / muscle contraction / negative regulation of cell growth / Z disc / actin filament binding / heart development / cytoskeleton / calmodulin binding / calcium ion binding / ATP binding / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||||||||
Authors | Grinzato A / Kandiah E / Robert-Paganin J / Auguin D / Kikuti C / Nandwani N / Moussaoui D / Pathak D / Ruppel KM / Spudich JA / Houdusse A | ||||||||||||
Funding support | United States, France, 3 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Cryo-EM structure of the folded-back state of human β-cardiac myosin. Authors: Alessandro Grinzato / Daniel Auguin / Carlos Kikuti / Neha Nandwani / Dihia Moussaoui / Divya Pathak / Eaazhisai Kandiah / Kathleen M Ruppel / James A Spudich / Anne Houdusse / Julien Robert-Paganin / Abstract: To save energy and precisely regulate cardiac contractility, cardiac muscle myosin heads are sequestered in an 'off' state that can be converted to an 'on' state when exertion is increased. The 'off' ...To save energy and precisely regulate cardiac contractility, cardiac muscle myosin heads are sequestered in an 'off' state that can be converted to an 'on' state when exertion is increased. The 'off' state is equated with a folded-back structure known as the interacting-heads motif (IHM), which is a regulatory feature of all class-2 muscle and non-muscle myosins. We report here the human β-cardiac myosin IHM structure determined by cryo-electron microscopy to 3.6 Å resolution, providing details of all the interfaces stabilizing the 'off' state. The structure shows that these interfaces are hot spots of hypertrophic cardiomyopathy mutations that are thought to cause hypercontractility by destabilizing the 'off' state. Importantly, the cardiac and smooth muscle myosin IHM structures dramatically differ, providing structural evidence for the divergent physiological regulation of these muscle types. The cardiac IHM structure will facilitate development of clinically useful new molecules that modulate IHM stability. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_15353.map.gz | 450.7 MB | EMDB map data format | |
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Header (meta data) | emd-15353-v30.xml emd-15353.xml | 19.1 KB 19.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_15353_fsc.xml | 17.3 KB | Display | FSC data file |
Images | emd_15353.png | 143 KB | ||
Masks | emd_15353_msk_1.map | 476.8 MB | Mask map | |
Others | emd_15353_half_map_1.map.gz emd_15353_half_map_2.map.gz | 442.7 MB 442.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-15353 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15353 | HTTPS FTP |
-Validation report
Summary document | emd_15353_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_15353_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_15353_validation.xml.gz | 25 KB | Display | |
Data in CIF | emd_15353_validation.cif.gz | 32.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15353 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15353 | HTTPS FTP |
-Related structure data
Related structure data | 8actMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_15353.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | density map of the IHMof b-cardiac myosin | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_15353_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map A of the IHMof b-cardiac myosin
File | emd_15353_half_map_1.map | ||||||||||||
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Annotation | half map A of the IHMof b-cardiac myosin | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B of the IHMof b-cardiac myosin
File | emd_15353_half_map_2.map | ||||||||||||
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Annotation | half map B of the IHMof b-cardiac myosin | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : human beta-cardiac myosin folded-back off state
Entire | Name: human beta-cardiac myosin folded-back off state |
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Components |
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-Supramolecule #1: human beta-cardiac myosin folded-back off state
Supramolecule | Name: human beta-cardiac myosin folded-back off state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Myosin-7
Macromolecule | Name: Myosin-7 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 103.807148 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DSEMAVFGAA APYLRKSEKE RLEAQTRPFD LKKDVFVPDD KQEFVKAKIV SREGGKVTAE TEYGKTVTVK EDQVMQQNPP KFDKIEDMA MLTFLHEPAV LYNLKDRYGS WMIYTYSGLF CVTVNPY(M3L)WL PVYTPEVVAA YRGKKRSEAP PHIFSIS DN AYQYMLTDRE ...String: DSEMAVFGAA APYLRKSEKE RLEAQTRPFD LKKDVFVPDD KQEFVKAKIV SREGGKVTAE TEYGKTVTVK EDQVMQQNPP KFDKIEDMA MLTFLHEPAV LYNLKDRYGS WMIYTYSGLF CVTVNPY(M3L)WL PVYTPEVVAA YRGKKRSEAP PHIFSIS DN AYQYMLTDRE NQSILITGES GAGKTVNTKR VIQYFAVIAA IGDRSKKDQS PGKGTLEDQI IQANPALEAF GNAKTVRN D NSSRFGKFIR IHFGATGKLA SADIETYLLE KSRVIFQLKA ERDYHIFYQI LSNKKPELLD MLLITNNPYD YAFISQGET TVASIDDAEE LMATDNAFDV LGFTSEEKNS MYKLTGAIMH FGNMKFKLKQ REEQAEPDGT EEADKSAYLM GLNSADLLKG LCHPRVKVG NEYVTKGQNV QQVIYATGAL AKAVYERMFN WMVTRINATL ETKQPRQYFI GVLDIAGFEI FDFNSFEQLC I NFTNEKLQ QFFNHHMFVL EQEEYKKEGI EWTFIDFGMD LQACIDLIEK PMGIMSILEE ECMFPKATDM TF(M3L)AKLFD N HLGKSANFQK PRNIKGKPEA HFSLIHYAGI VDYNIIGWLQ KNKDPLNETV VGLYQKSSLK LLSTLFANYA GADAPIEKG KGKAKKGSSF QTVSALHREN LNKLMTNLRS THPHFVRCII PNETKSPGVM DNPLVMHQLR CNGVLEGIRI CRKGFPNRIL YGDFRQRYR ILNPAAIPEG QFIDSRKGAE KLLSSLDIDH NQYKFGHTKV FFKAGLLGLL EEMRDERLSR IITRIQAQSR G VLARMEYK KLLERRDSLL VIQWNIRAFM GVKNWPWMKL YFKIKPLLKS AEREKEMASM KEEFTRLKEA LEKSEARRKE LE EKMVSLL QEKNDLQLQV QAEQDNLADA EERCD UniProtKB: Myosin-7 |
-Macromolecule #2: Myosin light chain 3
Macromolecule | Name: Myosin light chain 3 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 17.895398 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ASKIKIEFTP EQIEEFKEAF MLFDRTPKCE MKITYGQCGD VLRALGQNPT QAEVLRVLGK PRQEELNTKM MDFETFLPML QHISKNKDT GTYEDFVEGL RVFDKEGNGT VMGAELRHVL ATLGERLTED EVEKLMAGQE DSNGCINYEA FVKHIMSS 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: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 16.49058 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFEQTQIQEF KEAFTIMDQN RDGFIDKNDL RDTFAALGRV NVKNEEIDEM IKEAPGPINF TVFLTMFGEK LKGADPEETI LNAFKVFDP EGKGVLKADY VREMLTTQAE RFSKEEVDQM FAAFPPDVTG NLDYKNLVHI ITHGE UniProtKB: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform |
-Macromolecule #4: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ChemComp-ADP: |
-Macromolecule #5: PHOSPHATE ION
Macromolecule | Name: PHOSPHATE ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: PO4 |
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Molecular weight | Theoretical: 94.971 Da |
Chemical component information | ChemComp-PO4: |
-Macromolecule #6: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-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: 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 / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |