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Yorodumi- EMDB-37260: Cryo-EM structure of Myosin VI in the autoinhibited state (withou... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37260 | |||||||||
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Title | Cryo-EM structure of Myosin VI in the autoinhibited state (without SAH-extension density) | |||||||||
Map data | cryo-EM map of autoinhibited MyoVI without SAH-extension | |||||||||
Sample |
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Keywords | myosin VI / autoinhibition / intracellular transport / MOTOR PROTEIN | |||||||||
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 / RHO GTPases activate IQGAPs / Extra-nuclear estrogen signaling / RAF/MAP kinase cascade / PKA activation / actin filament-based movement / Platelet degranulation / inner ear auditory receptor cell differentiation / clathrin-coated vesicle membrane / 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 / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / microfilament motor activity / nitric-oxide synthase binding / protein phosphatase activator activity / cytoskeletal motor activity / filamentous actin / microvillus / RHOU GTPase cycle / adenylate cyclase binding / catalytic complex / DNA damage response, signal transduction by p53 class mediator / detection of calcium ion / regulation of cardiac muscle contraction / endocytic vesicle / negative regulation of ryanodine-sensitive calcium-release channel activity / autophagosome / 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 / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / voltage-gated potassium channel complex / 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 / positive regulation of receptor signaling pathway via JAK-STAT / intracellular protein transport / protein localization / spindle microtubule / ADP binding / ruffle membrane / cellular response to type II interferon / spindle pole / endocytosis / G2/M transition of mitotic cell cycle / calcium-dependent protein binding / actin filament binding / actin cytoskeleton / apical part of cell Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.54 Å | |||||||||
Authors | Niu F / Wei Z | |||||||||
Funding support | China, 2 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37260.map.gz | 284.3 MB | EMDB map data format | |
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Header (meta data) | emd-37260-v30.xml emd-37260.xml | 21.9 KB 21.9 KB | Display Display | EMDB header |
Images | emd_37260.png | 80.7 KB | ||
Filedesc metadata | emd-37260.cif.gz | 6.9 KB | ||
Others | emd_37260_half_map_1.map.gz emd_37260_half_map_2.map.gz | 301.5 MB 301.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37260 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37260 | HTTPS FTP |
-Validation report
Summary document | emd_37260_validation.pdf.gz | 817.9 KB | Display | EMDB validaton report |
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Full document | emd_37260_full_validation.pdf.gz | 817.5 KB | Display | |
Data in XML | emd_37260_validation.xml.gz | 16.8 KB | Display | |
Data in CIF | emd_37260_validation.cif.gz | 19.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37260 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37260 | HTTPS FTP |
-Related structure data
Related structure data | 8w41MC 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_37260.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | cryo-EM map of autoinhibited MyoVI without SAH-extension | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.827 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map B
File | emd_37260_half_map_1.map | ||||||||||||
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Annotation | half_map_B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_37260_half_map_2.map | ||||||||||||
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Annotation | half_map_A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of Myosin VI and Calmodulin
Entire | Name: Complex of Myosin VI and Calmodulin |
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Components |
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-Supramolecule #1: Complex of Myosin VI and Calmodulin
Supramolecule | Name: Complex of Myosin VI and Calmodulin / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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-Supramolecule #2: myosin VI
Supramolecule | Name: myosin VI / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: Calmodulin
Supramolecule | Name: Calmodulin / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Calmodulin-1
Macromolecule | Name: Calmodulin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 16.852545 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK UniProtKB: Calmodulin-1 |
-Macromolecule #2: Unconventional myosin-VI
Macromolecule | Name: Unconventional myosin-VI / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 148.952766 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE DNCSLMYLNE ATLLHNIKVR YSKDRIYTY VANILIAVNP YFDIPKIYSS EAIKSYQGKS LGTRPPHVFA IADKAFRDMK VLKMSQSIIV SGESGAGKTE N TKFVLRYL ...String: MEDGKPVWAP HPTDGFQMGN IVDIGPDSLT IEPLNQKGKT FLALINQVFP AEEDSKKDVE DNCSLMYLNE ATLLHNIKVR YSKDRIYTY VANILIAVNP YFDIPKIYSS EAIKSYQGKS LGTRPPHVFA IADKAFRDMK VLKMSQSIIV SGESGAGKTE N TKFVLRYL TESYGTGQDI DDRIVEANPL LEAFGNAKTV RNNNSSRFGK FVEIHFNEKS SVVGGFVSHY LLEKSRICVQ GK EERNYHI FYRLCAGASE DIREKLHLSS PDNFRYLNRG CTRYFANKET DKQILQNRKS PEYLKAGSMK DPLLDDHGDF IRM CTAMKK IGLDDEEKLD LFRVVAGVLH LGNIDFEEAG STSGGCNLKN KSAQSLEYCA ELLGLDQDDL RVSLTTRVML TTAG GTKGT VIKVPLKVEQ ANNARDALAK TVYSHLFDHV VNRVNQCFPF ETSSYFIGVL DIAGFEYFEH NSFEQFCINY CNEKL QQFF NERILKEEQE LYQKEGLGVN EVHYVDNQDC IDLIEAKLVG ILDILDEENR LPQPSDQHFT SAVHQKHKDH FRLTIP RKS KLAVHRNIRD DEGFIIRHFA GAVCYETTQF VEKNNDALHM SLESLICESR DKFIRELFES STNNNKDTKQ KAGKLSF IS VGNKFKTQLN LLLDKLRSTG ASFIRCIKPN LKMTSHHFEG AQILSQLQCS GMVSVLDLMQ GGYPSRASFH ELYNMYKK Y MPDKLARLDP RLFCKALFKA LGLNENDYKF GLTKVFFRPG KFAEFDQIMK SDPDHLAELV KRVNHWLTCS RWKKVQWCS LSVIKLKNKI KYRAEACIKM QKTIRMWLCK RRHKPRIDGL VKVGTLKKRL DKFNEVVSVL KDGKPEMNKQ IKNLEISIDT LMAKIKSTM MTQEQIQKEY DALVKSSEEL LSALQKKKQQ EEEAERLRRI QEEMEKERKR REEDEKRRRK EEEERRMKLE M EAKRKQEE EERKKREDDE KRIQAEVEAQ LARQKEEESQ QQAVLEQERR DRELALRIAQ SEAELISDEA QADLALRRND GT RPKMTPE QMAKEMSEFL SRGPAVLATK AAAGTKKYDL SKWKYAELRD TINTSCDIEL LAACREEFHR RLKVYHAWKS KNK KRNTET EQRAPKSVTD YDFAPFLNNS PQQNPAAQIP ARQREIEMNR QQRFFRIPFI RPADQYKDPQ SKKKGWWYAH FDGP WIARQ MELHPDKPPI LLVAGKDDME MCELNLEETG LTRKRGAEIL PRQFEEIWER CGGIQYLQNA IESRQARPTY ATAML QSLL K UniProtKB: Unconventional myosin-VI |
-Macromolecule #3: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #4: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 1 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ChemComp-ADP: |
-Macromolecule #5: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 5 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #6: PHOSPHATE ION
Macromolecule | Name: PHOSPHATE ION / type: ligand / ID: 6 / Number of copies: 1 / Formula: PO4 |
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Molecular weight | Theoretical: 94.971 Da |
Chemical component information | ChemComp-PO4: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 2.0 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT | ||||||||||||
Output model | PDB-8w41: |