+Open data
-Basic information
Entry | Database: PDB / ID: 8w41 | |||||||||
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Title | Cryo-EM structure of Myosin VI in the autoinhibited state | |||||||||
Components |
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Keywords | MOTOR PROTEIN / myosin VI / autoinhibition / intracellular transport | |||||||||
Function / homology | Function and homology information CaMK IV-mediated phosphorylation of CREB / Cam-PDE 1 activation / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Glycogen breakdown (glycogenolysis) / Activation of RAC1 downstream of NMDARs / Reduction of cytosolic Ca++ levels / Sodium/Calcium exchangers / Activation of Ca-permeable Kainate Receptor / CLEC7A (Dectin-1) induces NFAT activation / Synthesis of IP3 and IP4 in the cytosol ...CaMK IV-mediated phosphorylation of CREB / Cam-PDE 1 activation / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Glycogen breakdown (glycogenolysis) / Activation of RAC1 downstream of NMDARs / Reduction of cytosolic Ca++ levels / Sodium/Calcium exchangers / Activation of Ca-permeable Kainate Receptor / CLEC7A (Dectin-1) induces NFAT activation / Synthesis of IP3 and IP4 in the cytosol / RHO GTPases activate PAKs / Calmodulin induced events / Inactivation, recovery and regulation of the phototransduction cascade / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Calcineurin activates NFAT / eNOS activation / Ion transport by P-type ATPases / Unblocking of NMDA receptors, glutamate binding and activation / Protein methylation / regulation of secretion / RAF activation / VEGFR2 mediated vascular permeability / RAS processing / Smooth Muscle Contraction / minus-end directed microfilament motor activity / Ca2+ pathway / unconventional myosin complex / FCERI mediated Ca+2 mobilization / RAF/MAP kinase cascade / RHO GTPases activate IQGAPs / Extra-nuclear estrogen signaling / PKA activation / actin filament-based movement / Platelet degranulation / clathrin-coated vesicle membrane / inner ear auditory receptor cell differentiation / Gap junction degradation / Stimuli-sensing channels / Ion homeostasis / type 3 metabotropic glutamate receptor binding / vesicle transport along actin filament / Trafficking of AMPA receptors / RHOBTB1 GTPase cycle / organelle localization by membrane tethering / inner ear morphogenesis / microfilament motor activity / mitochondrion-endoplasmic reticulum membrane tethering / regulation of cardiac muscle cell action potential / autophagosome membrane docking / nitric-oxide synthase binding / protein phosphatase activator activity / filamentous actin / microvillus / cytoskeletal motor activity / RHOU GTPase cycle / adenylate cyclase binding / catalytic complex / DNA damage response, signal transduction by p53 class mediator / detection of calcium ion / endocytic vesicle / negative regulation of ryanodine-sensitive calcium-release channel activity / autophagosome / regulation of cardiac muscle contraction / calcium channel inhibitor activity / cellular response to interferon-beta / RHOBTB2 GTPase cycle / phosphatidylinositol 3-kinase binding / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / clathrin-coated pit / positive regulation of protein dephosphorylation / voltage-gated potassium channel complex / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / sperm midpiece / ruffle / calcium channel complex / adenylate cyclase activator activity / nitric-oxide synthase regulator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / regulation of cytokinesis / filopodium / actin filament / actin filament organization / sensory perception of sound / intracellular protein transport / positive regulation of receptor signaling pathway via JAK-STAT / spindle microtubule / protein localization / ADP binding / ruffle membrane / cellular response to type II interferon / spindle pole / endocytosis / calcium-dependent protein binding / G2/M transition of mitotic cell cycle / actin filament binding / actin cytoskeleton / apical part of cell Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.54 Å | |||||||||
Authors | Niu, F. / Wei, Z. | |||||||||
Funding support | China, 2items
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Citation | Journal: Nat Commun / Year: 2024 Title: Autoinhibition and activation of myosin VI revealed by its cryo-EM structure. Authors: Fengfeng Niu / Lingxuan Li / Lei Wang / Jinman Xiao / Shun Xu / Yong Liu / Leishu Lin / Cong Yu / Zhiyi Wei / Abstract: Myosin VI is the only molecular motor that moves towards the minus end along actin filaments. Numerous cellular processes require myosin VI and tight regulations of the motor's activity. Defects in ...Myosin VI is the only molecular motor that moves towards the minus end along actin filaments. Numerous cellular processes require myosin VI and tight regulations of the motor's activity. Defects in myosin VI activity are known to cause genetic diseases such as deafness and cardiomyopathy. However, the molecular mechanisms underlying the activity regulation of myosin VI remain elusive. Here, we determined the high-resolution cryo-electron microscopic structure of myosin VI in its autoinhibited state. Our structure reveals that autoinhibited myosin VI adopts a compact, monomeric conformation via extensive interactions between the head and tail domains, orchestrated by an elongated single-α-helix region resembling a "spine". This autoinhibited structure effectively blocks cargo binding sites and represses the motor's ATPase activity. Certain cargo adaptors such as GIPC can release multiple inhibitory interactions and promote motor activity, pointing to a cargo-mediated activation of the processive motor. Moreover, our structural findings allow rationalization of disease-associated mutations in myosin VI. Beyond the activity regulation mechanisms of myosin VI, our study also sheds lights on how activities of other myosin motors such as myosin VII and X might be regulated. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8w41.cif.gz | 275.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8w41.ent.gz | 216.7 KB | Display | PDB format |
PDBx/mmJSON format | 8w41.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w4/8w41 ftp://data.pdbj.org/pub/pdb/validation_reports/w4/8w41 | HTTPS FTP |
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-Related structure data
Related structure data | 37260MC 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
-Protein , 2 types, 3 molecules BIA
#1: Protein | Mass: 16852.545 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Calm1, Calm, Cam, Cam1 / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: P0DP26 #2: Protein | | Mass: 148952.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MYO6 / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: Q9UM54 |
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-Non-polymers , 4 types, 7 molecules
#3: Chemical | ChemComp-CA / #4: Chemical | ChemComp-ADP / | #5: Chemical | ChemComp-MG / | #6: Chemical | ChemComp-PO4 / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) / Cell: 293F | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 2 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 10544925 | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 173658 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
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