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Yorodumi- EMDB-34121: Cryo-EM structure of full-length Myosin Va in the autoinhibited state -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34121 | |||||||||
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Title | Cryo-EM structure of full-length Myosin Va in the autoinhibited state | |||||||||
Map data | overall_map | |||||||||
Sample |
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Keywords | intracellular trafficking / molecular motor / myosin / autoinhibition / 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 / RAF activation / VEGFR2 mediated vascular permeability / RAS processing / Ca2+ pathway / presynaptic endocytosis / FCERI mediated Ca+2 mobilization / Smooth Muscle Contraction / RHO GTPases activate IQGAPs / Extra-nuclear estrogen signaling / RAF/MAP kinase cascade / PKA activation / Platelet degranulation / Stimuli-sensing channels / Ion homeostasis / type 3 metabotropic glutamate receptor binding / myosin complex / organelle localization by membrane tethering / autophagosome membrane docking / mitochondrion-endoplasmic reticulum membrane tethering / regulation of cardiac muscle cell action potential / nitric-oxide synthase binding / negative regulation of ryanodine-sensitive calcium-release channel activity / adenylate cyclase activator activity / protein phosphatase activator activity / cytoskeletal motor activity / adenylate cyclase binding / calyx of Held / catalytic complex / regulation of cardiac muscle contraction / detection of calcium ion / regulation of ryanodine-sensitive calcium-release channel activity / cellular response to interferon-beta / calcium channel inhibitor activity / phosphatidylinositol 3-kinase binding / voltage-gated potassium channel complex / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / : / titin binding / sperm midpiece / calcium channel complex / nitric-oxide synthase regulator activity / sarcomere / regulation of heart rate / protein serine/threonine kinase activator activity / regulation of cytokinesis / spindle microtubule / positive regulation of receptor signaling pathway via JAK-STAT / cellular response to type II interferon / spindle pole / calcium-dependent protein binding / G2/M transition of mitotic cell cycle / protein transport / myelin sheath / actin binding / growth cone / transmembrane transporter binding / protein domain specific binding / centrosome / calcium ion binding / protein kinase binding / nucleoplasm / ATP binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.78 Å | |||||||||
Authors | Niu F / Wei Z | |||||||||
Funding support | China, 1 items
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Citation | Journal: Sci Adv / Year: 2022 Title: Autoinhibition and activation mechanisms revealed by the triangular-shaped structure of myosin Va. Authors: Fengfeng Niu / Yong Liu / Kang Sun / Shun Xu / Jiayuan Dong / Cong Yu / Kaige Yan / Zhiyi Wei / Abstract: As the prototype of unconventional myosin motor family, myosin Va (MyoVa) transport cellular cargos along actin filaments in diverse cellular processes. The off-duty MyoVa adopts a closed and ...As the prototype of unconventional myosin motor family, myosin Va (MyoVa) transport cellular cargos along actin filaments in diverse cellular processes. The off-duty MyoVa adopts a closed and autoinhibited state, which can be relieved by cargo binding. The molecular mechanisms governing the autoinhibition and activation of MyoVa remain unclear. Here, we report the cryo-electron microscopy structure of the two full-length, closed MyoVa heavy chains in complex with 12 calmodulin light chains at 4.78-Å resolution. The MyoVa adopts a triangular structure with multiple intra- and interpolypeptide chain interactions in establishing the closed state with cargo binding and adenosine triphosphatase activity inhibited. Structural, biochemical, and cellular analyses uncover an asymmetric autoinhibition mechanism, in which the cargo-binding sites in the two MyoVa heavy chains are differently protected. Thus, specific and efficient MyoVa activation requires coincident binding of multiple cargo adaptors, revealing an intricate and elegant activity regulation of the motor in response to cargos. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_34121.map.gz | 778.5 MB | EMDB map data format | |
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Header (meta data) | emd-34121-v30.xml emd-34121.xml | 27.4 KB 27.4 KB | Display Display | EMDB header |
Images | emd_34121.png | 97.7 KB | ||
Filedesc metadata | emd-34121.cif.gz | 7.3 KB | ||
Others | emd_34121_additional_1.map.gz emd_34121_additional_2.map.gz emd_34121_additional_3.map.gz emd_34121_half_map_1.map.gz emd_34121_half_map_2.map.gz | 778.3 MB 778.4 MB 1.8 MB 764.5 MB 764.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34121 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34121 | HTTPS FTP |
-Validation report
Summary document | emd_34121_validation.pdf.gz | 1015.1 KB | Display | EMDB validaton report |
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Full document | emd_34121_full_validation.pdf.gz | 1014.6 KB | Display | |
Data in XML | emd_34121_validation.xml.gz | 21 KB | Display | |
Data in CIF | emd_34121_validation.cif.gz | 25.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34121 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34121 | HTTPS FTP |
-Related structure data
Related structure data | 7yv9MC 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_34121.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | overall_map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.072 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: local map1
File | emd_34121_additional_1.map | ||||||||||||
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Annotation | local_map1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: local map2
File | emd_34121_additional_2.map | ||||||||||||
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Annotation | local_map2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: local map3
File | emd_34121_additional_3.map | ||||||||||||
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Annotation | local_map3 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half A map
File | emd_34121_half_map_1.map | ||||||||||||
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Annotation | half_A_map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half B map
File | emd_34121_half_map_2.map | ||||||||||||
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Annotation | half_B_map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Myosin Va and Calmodulin complex
Entire | Name: Myosin Va and Calmodulin complex |
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Components |
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-Supramolecule #1: Myosin Va and Calmodulin complex
Supramolecule | Name: Myosin Va and Calmodulin complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 630 KDa |
-Macromolecule #1: Unconventional myosin-Va
Macromolecule | Name: Unconventional myosin-Va / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 212.657359 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MAASELYTKF ARVWIPDPEE VWKSAELLKD YKPGDKVLLL HLEEGKDLEY RLDPKTGELP HLRNPDILVG ENDLTALSYL HEPAVLHNL RVRFIDSKLI YTYCGIVLVA INPYEQLPIY GEDIINAYSG QNMGDMDPHI FAVAEEAYKQ MARDERNQSI I VSGESGAG ...String: MAASELYTKF ARVWIPDPEE VWKSAELLKD YKPGDKVLLL HLEEGKDLEY RLDPKTGELP HLRNPDILVG ENDLTALSYL HEPAVLHNL RVRFIDSKLI YTYCGIVLVA INPYEQLPIY GEDIINAYSG QNMGDMDPHI FAVAEEAYKQ MARDERNQSI I VSGESGAG KTVSAKYAMR YFATVSGSAS EANVEEKVLA SNPIMESIGN AKTTRNDNSS RFGKYIEIGF DKRYRIIGAN MR TYLLEKS RVVFQAEEER NYHIFYQLCA SAKLPEFKML RLGNADSFHY TKQGGSPMIE GVDDAKEMAH TRQACTLLGI SES YQMGIF RILAGILHLG NVGFASRDSD SCTIPPKHEP LTIFCDLMGV DYEEMCHWLC HRKLATATET YIKPISKLQA TNAR DALAK HIYAKLFNWI VDHVNQALHS AVKQHSFIGV LDIYGFETFE INSFEQFCIN YANEKLQQQF NMHVFKLEQE EYMKE QIPW TLIDFYDNQP CINLIESKLG ILDLLDEECK MPKGTDDTWA QKLYNTHLNK CALFEKPRMS NKAFIIKHFA DKVEYQ CEG FLEKNKDTVF EEQIKVLKSS KFKMLPELFQ DDEKAISPTS ATSSGRTPLT RVPVKPTKGR PGQTAKEHKK TVGHQFR NS LHLLMETLNA TTPHYVRCIK PNDFKFPFTF DEKRAVQQLR ACGVLETIRI SAAGFPSRWT YQEFFSRYRV LMKQKDVL G DRKQTCKNVL EKLILDKDKY QFGKTKIFFR AGQVAYLEKL RADKLRAACI RIQKTIRGWL LRKRYLCMQR AAITVQRYV RGYQARCYAK FLRRTKAATT IQKYWRMYVV RRRYKIRRAA TIVIQSYLRG YLTRNRYRKI LREYKAVIIQ KRVRGWLART HYKRTMKAI VYLQCCFRRM MAKRELKKLK IEARSVERYK KLHIGMENKI MQLQRKVDEQ NKDYKCLMEK LTNLEGVYNS E TEKLRNDV ERLQLSEEEA KVATGRVLSL QEEIAKLRKD LEQTRSEKKS IEERADKYKQ ETDQLVSNLK EENTLLKQEK ET LNHRIVE QAKEMTETME RKLVEETKQL ELDLNDERLR YQNLLNEFSR LEERYDDLKE EMTLMLNVPK PGHKRTDSTH SSN ESEYTF SSEFAETEDI APRTEEPIEK KVPLDMSLFL KLQKRVTELE QEKQLMQDEL DRKEEQVFRS KAKEEERPQI RGAE LEYES LKRQELESEN KKLKNELNEL RKALSEKSAP EVTAPGAPAY RVLMEQLTSV SEELDVRKEE VLILRSQLVS QKEAI QPKD DKNTMTDSTI LLEDVQKMKD KGEIAQAYIG LKETNRLLES QLQSQKRSHE NEAEALRGEI QSLKEENNRQ QQLLAQ NLQ LPPEARIEAS LQHEITRLTN ENLDLMEQLE KQDKTVRKLK KQLKVFAKKI GELEVGQMEN ISPGQIIDEP IRPVNIP RK EKDFQGMLEY KREDEQKLVK NLILELKPRG VAVNLIPGLP AYILFMCVRH ADYLNDDQKV RSLLTSTINS IKKVLKKR G DDFETVSFWL SNTCRFLHCL KQYSGEEGFM KHNTSRQNEH CLTNFDLAEY RQVLSDLAIQ IYQQLVRVLE NILQPMIVS GMLEHETIQG VSGVKPTGLR KRTSSIADEG TYTLDSILRQ LNSFHSVMCQ HGMDPELIKQ VVKQMFYIVG AITLNNLLLR KDMCSWSKG MQIRYNVSQL EEWLRDKNLM NSGAKETLEP LIQAAQLLQV KKKTDDDAEA ICSMCNALTT AQIVKVLNLY T PVNEFEER VSVSFIRTIQ MRLRDRKDSP QLLMDAKHIF PVTFPFNPSS LALETIQIPA SLGLGFIARV UniProtKB: Myosin VA |
-Macromolecule #2: Calmodulin-1
Macromolecule | Name: Calmodulin-1 / type: protein_or_peptide / ID: 2 / Number of copies: 12 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 16.848605 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KQLGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPQFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAQLRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EQFVQMMTAK UniProtKB: Calmodulin-1 |
-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: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. | ||||||||||||||||||
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 / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
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: OTHER / Overall B value: 167.3 / Target criteria: Correlation coefficient | ||||||||
Output model | PDB-7yv9: |