[English] 日本語
Yorodumi
- EMDB-73283: Cryo-EM structure of human beta-cardiac myosin bound to omecamtiv... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-73283
TitleCryo-EM structure of human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state
Map data
Sample
  • Complex: Human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state
    • Complex: Myosin-7
      • Protein or peptide: Myosin-7,General control transcription factor GCN4,Enhanced Green fluorescent protein
    • Complex: Myosin light chain 1/3 and Myosin regulatory light chain 11
      • Protein or peptide: Myosin light chain 1/3, skeletal muscle isoform
      • Protein or peptide: Myosin regulatory light chain 11
  • Ligand: methyl 4-(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}benzyl)piperazine-1-carboxylate
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: PHOSPHATE ION
KeywordsCardiac Myosin / Interacting Heads Motif / Omecamtiv Mecarbil / Actin Binding / CONTRACTILE PROTEIN
Function / homology
Function and homology information


regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / unconventional myosin complex / Striated Muscle Contraction / contractile muscle fiber / Smooth Muscle Contraction / FCERI mediated MAPK activation / protein localization to nuclear periphery / muscle myosin complex / Activation of the AP-1 family of transcription factors ...regulation of slow-twitch skeletal muscle fiber contraction / regulation of the force of skeletal muscle contraction / unconventional myosin complex / Striated Muscle Contraction / contractile muscle fiber / Smooth Muscle Contraction / FCERI mediated MAPK activation / protein localization to nuclear periphery / muscle myosin complex / Activation of the AP-1 family of transcription factors / negative regulation of ribosomal protein gene transcription by RNA polymerase II / positive regulation of cellular response to amino acid starvation / response to amino acid starvation / mediator complex binding / regulation of the force of heart contraction / transition between fast and slow fiber / myosin filament / Oxidative Stress Induced Senescence / cardiac muscle hypertrophy in response to stress / muscle filament sliding / myosin complex / adult heart development / myosin II complex / structural constituent of muscle / ventricular cardiac muscle tissue morphogenesis / microfilament motor activity / myofibril / amino acid biosynthetic process / cytoskeletal motor activity / TFIID-class transcription factor complex binding / positive regulation of RNA polymerase II transcription preinitiation complex assembly / positive regulation of transcription initiation by RNA polymerase II / skeletal muscle tissue development / ATP metabolic process / striated muscle contraction / skeletal muscle contraction / cardiac muscle contraction / stress fiber / regulation of heart rate / cellular response to nutrient levels / muscle contraction / cellular response to amino acid starvation / bioluminescence / sarcomere / generation of precursor metabolites and energy / RNA polymerase II transcription regulator complex / Z disc / actin filament binding / DNA-binding transcription activator activity, RNA polymerase II-specific / transcription regulator complex / sequence-specific DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / DNA-binding transcription factor activity, RNA polymerase II-specific / calmodulin binding / intracellular signal transduction / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / calcium ion binding / chromatin binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / ATP binding / identical protein binding / nucleus / cytoplasm
Similarity search - Function
: / EF-hand domain / : / Basic region leucine zipper / DNA repair protein XRCC4-like, C-terminal / Myosin tail / Myosin tail / Myosin N-terminal SH3-like domain / Myosin S1 fragment, N-terminal / Basic-leucine zipper (bZIP) domain signature. ...: / EF-hand domain / : / Basic region leucine zipper / DNA repair protein XRCC4-like, C-terminal / Myosin tail / Myosin tail / Myosin N-terminal SH3-like domain / Myosin S1 fragment, N-terminal / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain / Basic-leucine zipper domain superfamily / Myosin, N-terminal, SH3-like / Myosin N-terminal SH3-like domain profile. / Short calmodulin-binding motif containing conserved Ile and Gln residues. / IQ motif, EF-hand binding site / Myosin motor domain profile. / Myosin head, motor domain / Myosin head (motor domain) / Myosin. Large ATPases. / IQ motif profile. / Kinesin motor domain superfamily / : / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / 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
General control transcription factor GCN4 / Myosin light chain 1/3, skeletal muscle isoform / Myosin-7 / Green fluorescent protein / Myosin regulatory light chain 11
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse) / Aequorea victoria (jellyfish)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.5 Å
AuthorsSomavarapu AK / Craig R / Padron R
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL164560 United States
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)AR081941 United States
CitationJournal: Sci Adv / Year: 2026
Title: Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.
Authors: Arun Kumar Somavarapu / Jinghua Ge / Christopher M Yengo / Roger Craig / Raul Padron /
Abstract: Genetic mutations in myosin, the motor protein that powers the heartbeat, are linked to inherited hypertrophic and dilated cardiomyopathies. Mavacamten and omecamtiv mecarbil are therapeutic, myosin- ...Genetic mutations in myosin, the motor protein that powers the heartbeat, are linked to inherited hypertrophic and dilated cardiomyopathies. Mavacamten and omecamtiv mecarbil are therapeutic, myosin-targeted drugs designed to treat these myopathies, but their mechanism of action has remained unclear. Using single-particle cryo-EM, we determined near-atomic resolution structures of wild-type, mavacamten-bound, and omecamtiv mecarbil-bound myosin molecules. Across all conditions, we observe two distinct, alternate conformations of myosin, not previously reported. We show how mavacamten stabilizes one conformation by reinforcing key electrostatic interfaces in the molecule, whereas omecamtiv mecarbil weakens these interfaces, favoring the second structure. This remodeling elucidates previously unclear allosteric mechanisms through which these drugs either inhibit or enhance myosin activity, countering the deleterious impacts of disease. These findings reveal how drugs modulate myosin structure to control cardiac contractility.
History
DepositionOct 13, 2025-
Header (metadata) releaseApr 8, 2026-
Map releaseApr 8, 2026-
UpdateMay 20, 2026-
Current statusMay 20, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_73283.png

Downloads & links

-
Map

FileDownload / File: emd_73283.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 400 pix.
= 332. Å		0.83 Å/pix.
x 400 pix.
= 332. Å		0.83 Å/pix.
x 400 pix.
= 332. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.16693689 - 0.359061
Average (Standard dev.)0.00042016417 (±0.010705387)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 332.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_73283_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_73283_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_73283_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human beta-cardiac myosin bound to omecamtiv mecarbil in the inte...

EntireName: Human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state
Components
  • Complex: Human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state
    • Complex: Myosin-7
      • Protein or peptide: Myosin-7,General control transcription factor GCN4,Enhanced Green fluorescent protein
    • Complex: Myosin light chain 1/3 and Myosin regulatory light chain 11
      • Protein or peptide: Myosin light chain 1/3, skeletal muscle isoform
      • Protein or peptide: Myosin regulatory light chain 11
  • Ligand: methyl 4-(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}benzyl)piperazine-1-carboxylate
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: PHOSPHATE ION

-
Supramolecule #1: Human beta-cardiac myosin bound to omecamtiv mecarbil in the inte...

SupramoleculeName: Human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Molecular weightTheoretical: 116.52168 KDa

-
Supramolecule #2: Myosin-7

SupramoleculeName: Myosin-7 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: Myosin light chain 1/3 and Myosin regulatory light chain 11

SupramoleculeName: Myosin light chain 1/3 and Myosin regulatory light chain 11
type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Mus musculus (house mouse)

-
Macromolecule #1: Myosin-7,General control transcription factor GCN4,Enhanced Green...

MacromoleculeName: Myosin-7,General control transcription factor GCN4,Enhanced Green fluorescent protein
type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Aequorea victoria (jellyfish)
Molecular weightTheoretical: 150.6565 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: MGDSEMAVFG AAAPYLRKSE KERLEAQTRP FDLKKDVFVP DDKQEFVKAK IVSREGGKVT AETEYGKTVT VKEDQVMQQN PPKFDKIED MAMLTFLHEP AVLYNLKDRY GSWMIYTYSG LFCVTVNPYK WLPVYTPEVV AAYRGKKRSE APPHIFSISD N AYQYMLTD ...String:
MGDSEMAVFG AAAPYLRKSE KERLEAQTRP FDLKKDVFVP DDKQEFVKAK IVSREGGKVT AETEYGKTVT VKEDQVMQQN PPKFDKIED MAMLTFLHEP AVLYNLKDRY GSWMIYTYSG LFCVTVNPYK WLPVYTPEVV AAYRGKKRSE APPHIFSISD N AYQYMLTD RENQSILITG ESGAGKTVNT KRVIQYFAVI AAIGDRSKKD QSPGKGTLED QIIQANPALE AFGNAKTVRN DN SSRFGKF IRIHFGATGK LASADIETYL LEKSRVIFQL KAERDYHIFY QILSNKKPEL LDMLLITNNP YDYAFISQGE TTV ASIDDA EELMATDNAF DVLGFTSEEK NSMYKLTGAI MHFGNMKFKL KQREEQAEPD GTEEADKSAY LMGLNSADLL KGLC HPRVK VGNEYVTKGQ NVQQVIYATG ALAKAVYERM FNWMVTRINA TLETKQPRQY FIGVLDIAGF EIFDFNSFEQ LCINF TNEK LQQFFNHHMF VLEQEEYKKE GIEWTFIDFG MDLQACIDLI EKPMGIMSIL EEECMFPKAT DMTFKAKLFD NHLGKS ANF QKPRNIKGKP EAHFSLIHYA GIVDYNIIGW LQKNKDPLNE TVVGLYQKSS LKLLSTLFAN YAGADAPIEK GKGKAKK GS SFQTVSALHR ENLNKLMTNL RSTHPHFVRC IIPNETKSPG VMDNPLVMHQ LRCNGVLEGI RICRKGFPNR ILYGDFRQ R YRILNPAAIP EGQFIDSRKG AEKLLSSLDI DHNQYKFGHT KVFFKAGLLG LLEEMRDERL SRIITRIQAQ SRGVLARME YKKLLERRDS LLVIQWNIRA FMGVKNWPWM KLYFKIKPLL KSAEREKEMA SMKEEFTRLK EALEKSEARR KELEEKMVSL LQEKNDLQL QVQAEQDNLA DAEERCDQLI KNKIQLEAKV KEMNERLEDE EEMNAELTAK KRKLEDECSE LKRDIDDLEL T LAKVEKEK HATENKVKNL TEEMAGLDEI IAKLTKEKKA LQEAHQQALD DLQAEEDKMK QLEDKVEELL SKNYHLENEV AR LKKLVGE RGSGKLGVSK GEELFTGVVP ILVELDGDVN GHKFSVSGEG EGDATYGKLT LKFICTTGKL PVPWPTLVTT LTY GVQCFS RYPDHMKQHD FFKSAMPEGY VQERTIFFKD DGNYKTRAEV KFEGDTLVNR IELKGIDFKE DGNILGHKLE YNYN SHNVY IMADKQKNGI KVNFKIRHNI EDGSVQLADH YQQNTPIGDG PVLLPDNHYL STQSALSKDP NEKRDHMVLL EFVTA AGIT LGMDELYKGL NDIFEAQKIE WHEDYKDDDD K

UniProtKB: Myosin-7, General control transcription factor GCN4, Green fluorescent protein

-
Macromolecule #2: Myosin light chain 1/3, skeletal muscle isoform

MacromoleculeName: Myosin light chain 1/3, skeletal muscle isoform / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 20.62049 KDa
SequenceString:
MAPKKDVKKP AAAPAPAPAP APAPAKPKEE KIDLSAIKIE FSKEQQEDFK EAFLLFDRTG ECKITLSQVG DVLRALGTNP TNAEVKKVL GNPSNEEMNA KKIEFEQFLP MMQAISNNKD QGGYEDFVEG LRVFDKEGNG TVMGAELRHV LATLGEKMKE E EVEALLAG QEDSNGCINY EAFVKHIMSV

UniProtKB: Myosin light chain 1/3, skeletal muscle isoform

-
Macromolecule #3: Myosin regulatory light chain 11

MacromoleculeName: Myosin regulatory light chain 11 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 18.978445 KDa
SequenceString:
MAPKKAKRRA GAEGSSNVFS MFDQTQIQEF KEAFTVIDQN RDGIIDKEDL RDTFAAMGRL NVKNEELDAM MKEASGPINF TVFLTMFGE KLKGADPEDV ITGAFKVLDP EGKGTIKKQF LEELLTTQCD RFSQEEIKNM WAAFPPDVGG NVDYKNICYV I THGDAKDQ E

UniProtKB: Myosin regulatory light chain 11

-
Macromolecule #4: methyl 4-(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}benz...

MacromoleculeName: methyl 4-(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}benzyl)piperazine-1-carboxylate
type: ligand / ID: 4 / Number of copies: 2 / Formula: 2OW
Molecular weightTheoretical: 401.435 Da
Chemical component information

ChemComp-2OW:
methyl 4-(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}benzyl)piperazine-1-carboxylate

-
Macromolecule #5: ADENOSINE-5'-DIPHOSPHATE

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

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

-
Macromolecule #6: PHOSPHATE ION

MacromoleculeName: PHOSPHATE ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: PO4
Molecular weightTheoretical: 94.971 Da
Chemical component information

ChemComp-PO4:
PHOSPHATE ION

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.5 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8act

Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 19218
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: cryoSPARC
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

8act


Chain - Residue range: 4-875 / Chain - Source name: PDB / Chain - Initial model type: experimental model
SoftwareName: UCSF ChimeraX
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-9yp4:
Cryo-EM structure of human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state

-
Atomic model buiding 2

Initial modelPDB ID:

2fxm


Chain - Residue range: 838-943 / Chain - Source name: PDB / Chain - Initial model type: experimental model
SoftwareName: UCSF ChimeraX
Output model

PDB-9yp4:
Cryo-EM structure of human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state

+
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