[English] 日本語
Yorodumi
- EMDB-15353: structure of the human beta-cardiac myosin folded-back off state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-15353
Titlestructure of the human beta-cardiac myosin folded-back off state
Map datadensity map of the IHMof b-cardiac myosin
Sample
  • Complex: human beta-cardiac myosin folded-back off state
    • Protein or peptide: Myosin-7
    • Protein or peptide: Myosin light chain 3
    • Protein or peptide: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: PHOSPHATE IONPhosphate
  • Ligand: MAGNESIUM ION
KeywordsCardiac 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 / muscle myosin complex / regulation of striated muscle contraction / cardiac myofibril assembly / muscle filament sliding / regulation of the force of heart contraction ...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 / muscle myosin complex / regulation of striated muscle contraction / cardiac myofibril assembly / muscle filament sliding / regulation of the force of heart contraction / transition between fast and slow fiber / myosin filament / myosin II complex / adult heart development / cardiac muscle hypertrophy in response to stress / Striated Muscle Contraction / positive regulation of ATP-dependent activity / I band / myosin complex / A band / structural constituent of muscle / sarcomere organization / microfilament motor activity / ventricular cardiac muscle tissue morphogenesis / myofibril / myosin heavy chain binding / heart contraction / positive regulation of the force of heart contraction / skeletal muscle contraction / actin monomer binding / striated muscle contraction / stress fiber / ATP metabolic process / cardiac muscle contraction / 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 / cytosol / cytoplasm
Similarity search - Function
DNA repair protein XRCC4-like, C-terminal / Myosin tail / Myosin tail / Myosin N-terminal SH3-like domain / Myosin S1 fragment, N-terminal / Myosin, N-terminal, SH3-like / Myosin N-terminal SH3-like domain profile. / Short calmodulin-binding motif containing conserved Ile and Gln residues. / Myosin head, motor domain / Myosin head (motor domain) ...DNA repair protein XRCC4-like, C-terminal / Myosin tail / Myosin tail / Myosin N-terminal SH3-like domain / Myosin S1 fragment, N-terminal / Myosin, N-terminal, SH3-like / Myosin N-terminal SH3-like domain profile. / Short calmodulin-binding motif containing conserved Ile and Gln residues. / Myosin head, motor domain / Myosin head (motor domain) / Myosin motor domain profile. / Myosin. Large ATPases. / IQ motif profile. / IQ motif, EF-hand binding site / Kinesin motor domain superfamily / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / EF-hand domain pair / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Myosin light chain 3 / Myosin regulatory light chain 2, ventricular/cardiac muscle isoform / Myosin-7
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsGrinzato 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
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)NIH-RM1GM131981-01 United States
Agence Nationale de la Recherche (ANR)ANR-21-CE11-0022-01 France
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)NIH-R01GM33289 United States
CitationJournal: 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
DepositionJul 6, 2022-
Header (metadata) releaseJun 7, 2023-
Map releaseJun 7, 2023-
UpdateAug 30, 2023-
Current statusAug 30, 2023Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_15353.png

Downloads & links

-
Map

FileDownload / File: emd_15353.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationdensity map of the IHMof b-cardiac myosin
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.84 Å/pix.
x 500 pix.
= 420. Å		0.84 Å/pix.
x 500 pix.
= 420. Å		0.84 Å/pix.
x 500 pix.
= 420. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.84 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-0.35962492 - 1.04705
Average (Standard dev.)-0.00044980226 (±0.023797013)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions500500500
Spacing500500500
CellA=B=C: 420.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_15353_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half map A of the IHMof b-cardiac myosin

Fileemd_15353_half_map_1.map
Annotationhalf map A of the IHMof b-cardiac myosin
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: half map B of the IHMof b-cardiac myosin

Fileemd_15353_half_map_2.map
Annotationhalf map B of the IHMof b-cardiac myosin
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human beta-cardiac myosin folded-back off state

EntireName: human beta-cardiac myosin folded-back off state
Components
  • Complex: human beta-cardiac myosin folded-back off state
    • Protein or peptide: Myosin-7
    • Protein or peptide: Myosin light chain 3
    • Protein or peptide: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: PHOSPHATE IONPhosphate
  • Ligand: MAGNESIUM ION

-
Supramolecule #1: human beta-cardiac myosin folded-back off state

SupramoleculeName: human beta-cardiac myosin folded-back off state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Myosin-7

MacromoleculeName: Myosin-7 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 103.807148 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

MacromoleculeName: Myosin light chain 3 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 17.895398 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
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

MacromoleculeName: Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.49058 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
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

MacromoleculeName: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: ADP
Molecular weightTheoretical: 427.201 Da
Chemical component information

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

-
Macromolecule #5: PHOSPHATE ION

MacromoleculeName: PHOSPHATE ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: PO4
Molecular weightTheoretical: 94.971 Da
Chemical component information

ChemComp-PO4:
PHOSPHATE ION / Phosphate

-
Macromolecule #6: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: MG
Molecular weightTheoretical: 24.305 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.3 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 40.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER
Details: The coiled-coil S2 region was fitted from the crystal structure (Blankenfeldt et al., 2006; PDB code 2FXM). The IQ2/RLC region was obtained by homology modeling based on the SmMyo2 IHM ...Details: The coiled-coil S2 region was fitted from the crystal structure (Blankenfeldt et al., 2006; PDB code 2FXM). The IQ2/RLC region was obtained by homology modeling based on the SmMyo2 IHM (Heissler et al., 2021; PDB code 7MF3).
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 213596
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more