+Open data
-Basic information
Entry | Database: PDB / ID: 8g4l | |||||||||||||||
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Title | Cryo-EM structure of the human cardiac myosin filament | |||||||||||||||
Components |
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Keywords | CONTRACTILE PROTEIN / cardiac / myosin / filament / complex | |||||||||||||||
Function / homology | Function and homology information myosin II heavy chain binding / C zone / regulation of muscle filament sliding / muscle cell fate specification / regulation of slow-twitch skeletal muscle fiber contraction / striated muscle myosin thick filament / regulation of the force of skeletal muscle contraction / sarcomerogenesis / structural molecule activity conferring elasticity / telethonin binding ...myosin II heavy chain binding / C zone / regulation of muscle filament sliding / muscle cell fate specification / regulation of slow-twitch skeletal muscle fiber contraction / striated muscle myosin thick filament / regulation of the force of skeletal muscle contraction / sarcomerogenesis / structural molecule activity conferring elasticity / telethonin binding / skeletal muscle myosin thick filament assembly / cardiac myofibril / muscle myosin complex / regulation of striated muscle contraction / cardiac myofibril assembly / muscle filament sliding / detection of muscle stretch / muscle alpha-actinin binding / regulation of the force of heart contraction / transition between fast and slow fiber / myosin filament / cardiac muscle tissue morphogenesis / regulation of catalytic activity / myosin II complex / adult heart development / cardiac muscle hypertrophy in response to stress / Striated Muscle Contraction / mitotic chromosome condensation / positive regulation of ATP-dependent activity / cardiac muscle hypertrophy / M band / actinin binding / I band / cardiac muscle cell development / regulation of protein kinase activity / myosin complex / A band / structural constituent of muscle / sarcomere organization / microfilament motor activity / ventricular cardiac muscle tissue morphogenesis / myosin binding / myofibril / myosin heavy chain binding / heart contraction / ATPase activator activity / positive regulation of the force of heart contraction / skeletal muscle thin filament assembly / striated muscle thin filament / skeletal muscle contraction / actin monomer binding / striated muscle contraction / heart morphogenesis / stress fiber / ATP metabolic process / protein kinase A signaling / titin binding / cardiac muscle contraction / regulation of heart rate / sarcomere / muscle contraction / condensed nuclear chromosome / positive regulation of protein secretion / negative regulation of cell growth / Z disc / response to calcium ion / : / actin filament binding / Platelet degranulation / actin binding / heart development / protein tyrosine kinase activity / protease binding / cytoskeleton / calmodulin binding / non-specific serine/threonine protein kinase / cell adhesion / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / calcium ion binding / positive regulation of gene expression / protein kinase binding / enzyme binding / extracellular exosome / extracellular region / ATP binding / identical protein binding / metal ion binding / cytosol / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.4 Å | |||||||||||||||
Authors | Dutta, D. / Nguyen, V. / Padron, R. / Craig, R. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nature / Year: 2023 Title: Cryo-EM structure of the human cardiac myosin filament. Authors: Debabrata Dutta / Vu Nguyen / Kenneth S Campbell / Raúl Padrón / Roger Craig / Abstract: Pumping of the heart is powered by filaments of the motor protein myosin that pull on actin filaments to generate cardiac contraction. In addition to myosin, the filaments contain cardiac myosin- ...Pumping of the heart is powered by filaments of the motor protein myosin that pull on actin filaments to generate cardiac contraction. In addition to myosin, the filaments contain cardiac myosin-binding protein C (cMyBP-C), which modulates contractility in response to physiological stimuli, and titin, which functions as a scaffold for filament assembly. Myosin, cMyBP-C and titin are all subject to mutation, which can lead to heart failure. Despite the central importance of cardiac myosin filaments to life, their molecular structure has remained a mystery for 60 years. Here we solve the structure of the main (cMyBP-C-containing) region of the human cardiac filament using cryo-electron microscopy. The reconstruction reveals the architecture of titin and cMyBP-C and shows how myosin's motor domains (heads) form three different types of motif (providing functional flexibility), which interact with each other and with titin and cMyBP-C to dictate filament architecture and function. The packing of myosin tails in the filament backbone is also resolved. The structure suggests how cMyBP-C helps to generate the cardiac super-relaxed state; how titin and cMyBP-C may contribute to length-dependent activation; and how mutations in myosin and cMyBP-C might disturb interactions, causing disease. The reconstruction resolves past uncertainties and integrates previous data on cardiac muscle structure and function. It provides a new paradigm for interpreting structural, physiological and clinical observations, and for the design of potential therapeutic drugs. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8g4l.cif.gz | 21.3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8g4l.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8g4l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g4/8g4l ftp://data.pdbj.org/pub/pdb/validation_reports/g4/8g4l | HTTPS FTP |
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-Related structure data
Related structure data | 29722MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 223445.984 Da / Num. of mol.: 78 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: heart / References: UniProt: P12883 #2: Protein | Mass: 21962.068 Da / Num. of mol.: 18 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: heart / References: UniProt: P08590 #3: Protein | Mass: 18813.273 Da / Num. of mol.: 18 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: heart / References: UniProt: P10916 #4: Protein | Mass: 119771.961 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: heart References: UniProt: Q8WZ42, non-specific serine/threonine protein kinase #5: Protein | Mass: 140947.172 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: heart / References: UniProt: Q14896 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Myosin filaments isolated from human cardiac left ventricular muscle Type: TISSUE / Entity ID: all / Source: NATURAL |
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Molecular weight | Value: 5.9 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 6.8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 61 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 6.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 102581 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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Atomic model building |
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