[English] 日本語
Yorodumi
- EMDB-25914: Cardiac thin filament decorated with regulatory M-domain of cardi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-25914
TitleCardiac thin filament decorated with regulatory M-domain of cardiac myosin binding protein C
Map datacardiac thin filament decorated with THM of regulatory M-domain of cMyBP-C
Sample
  • Complex: Complex of cardiac thin filament with C1-M fragment of cardiac myosin binding protein C (cMyBP-C)
    • Protein or peptide: cardiac actin
    • Protein or peptide: Myosin-binding protein C, cardiac-type
    • Protein or peptide: tropomyosin model
Function / homology
Function and homology information


C zone / regulation of muscle filament sliding / striated muscle myosin thick filament / cardiac myofibril / regulation of striated muscle contraction / A band / Striated Muscle Contraction / myosin binding / ventricular cardiac muscle tissue morphogenesis / positive regulation of ATP-dependent activity ...C zone / regulation of muscle filament sliding / striated muscle myosin thick filament / cardiac myofibril / regulation of striated muscle contraction / A band / Striated Muscle Contraction / myosin binding / ventricular cardiac muscle tissue morphogenesis / positive regulation of ATP-dependent activity / structural constituent of muscle / myosin heavy chain binding / ATPase activator activity / cardiac muscle contraction / heart morphogenesis / titin binding / sarcomere / actin binding / cell adhesion / metal ion binding / identical protein binding / cytosol
Similarity search - Function
MyBP-C, tri-helix bundle domain / Tri-helix bundle domain / Actins signature 1. / Actin, conserved site / Actins signature 2. / Actin/actin-like conserved site / Actins and actin-related proteins signature. / Actin / Actin family / Actin ...MyBP-C, tri-helix bundle domain / Tri-helix bundle domain / Actins signature 1. / Actin, conserved site / Actins signature 2. / Actin/actin-like conserved site / Actins and actin-related proteins signature. / Actin / Actin family / Actin / Immunoglobulin I-set / Immunoglobulin I-set domain / Fibronectin type III domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / ATPase, nucleotide binding domain / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
ACTA protein / Myosin-binding protein C, cardiac-type
Similarity search - Component
Biological speciespig (pig) / Homo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 8.0 Å
AuthorsRisi CM / Galkin VE
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL140925 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM116790 United States
CitationJournal: J Mol Biol / Year: 2022
Title: Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.
Authors: Cristina M Risi / Edwin Villanueva / Betty Belknap / Rachel L Sadler / Samantha P Harris / Howard D White / Vitold E Galkin /
Abstract: Cardiac myosin binding protein C (cMyBP-C) modulates cardiac contraction via direct interactions with cardiac thick (myosin) and thin (actin) filaments (cTFs). While its C-terminal domains (e.g. C8- ...Cardiac myosin binding protein C (cMyBP-C) modulates cardiac contraction via direct interactions with cardiac thick (myosin) and thin (actin) filaments (cTFs). While its C-terminal domains (e.g. C8-C10) anchor cMyBP-C to the backbone of the thick filament, its N-terminal domains (NTDs) (e.g. C0, C1, M, and C2) bind to both myosin and actin to accomplish its dual roles of inhibiting thick filaments and activating cTFs. While the positions of C0, C1 and C2 on cTF have been reported, the binding site of the M-domain on the surface of the cTF is unknown. Here, we used cryo-EM to reveal that the M-domain interacts with actin via helix 3 of its ordered tri-helix bundle region, while the unstructured part of the M-domain does not maintain extensive interactions with actin. We combined the recently obtained structure of the cTF with the positions of all the four NTDs on its surface to propose a complete model of the NTD binding to the cTF. The model predicts that the interactions of the NTDs with the cTF depend on the activation state of the cTF. At the peak of systole, when bound to the extensively activated cTF, NTDs would inhibit actomyosin interactions. In contrast, at falling Ca levels, NTDs would not compete with the myosin heads for binding to the cTF, but would rather promote formation of active cross-bridges at the adjacent regulatory units located at the opposite cTF strand. Our structural data provides a testable model of the cTF regulation by the cMyBP-C.
History
DepositionJan 14, 2022-
Header (metadata) releaseNov 23, 2022-
Map releaseNov 23, 2022-
UpdateDec 7, 2022-
Current statusDec 7, 2022Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_25914.map.gz / Format: CCP4 / Size: 4.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationcardiac thin filament decorated with THM of regulatory M-domain of cMyBP-C
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.35 Å/pix.
x 199 pix.
= 267.655 Å
1.35 Å/pix.
x 74 pix.
= 99.53 Å
1.35 Å/pix.
x 75 pix.
= 100.875 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

generated in cubic-lattice coordinate

Voxel sizeX=Y=Z: 1.345 Å
Density
Contour LevelBy AUTHOR: 0.728
Minimum - Maximum-2.7973177 - 10.353523
Average (Standard dev.)-3.2470252e-11 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions7475199
Spacing7574199
CellA: 100.875 Å / B: 99.53 Å / C: 267.655 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : Complex of cardiac thin filament with C1-M fragment of cardiac my...

EntireName: Complex of cardiac thin filament with C1-M fragment of cardiac myosin binding protein C (cMyBP-C)
Components
  • Complex: Complex of cardiac thin filament with C1-M fragment of cardiac myosin binding protein C (cMyBP-C)
    • Protein or peptide: cardiac actin
    • Protein or peptide: Myosin-binding protein C, cardiac-type
    • Protein or peptide: tropomyosin model

-
Supramolecule #1: Complex of cardiac thin filament with C1-M fragment of cardiac my...

SupramoleculeName: Complex of cardiac thin filament with C1-M fragment of cardiac myosin binding protein C (cMyBP-C)
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all
Details: Only triple helix motif of the M-domain is visible in the map. C1 domain is not bound and hence not visible in the map.

-
Macromolecule #1: cardiac actin

MacromoleculeName: cardiac actin / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: pig (pig) / Organ: heart / Tissue: cardiac muscle
Molecular weightTheoretical: 41.830551 KDa
SequenceString: DDEETTALVC DNGSGLVKAG FAGDDAPRAV FPSIVGRPRH QGVMVGMGQK DSYVGDEAQS KRGILTLKYP IEHGIITNWD DMEKIWHHT FYNELRVAPE EHPTLLTEAP LNPKANREKM TQIMFETFNV PAMYVAIQAV LSLYASGRTT GIVLDSGDGV T HNVPIYEG ...String:
DDEETTALVC DNGSGLVKAG FAGDDAPRAV FPSIVGRPRH QGVMVGMGQK DSYVGDEAQS KRGILTLKYP IEHGIITNWD DMEKIWHHT FYNELRVAPE EHPTLLTEAP LNPKANREKM TQIMFETFNV PAMYVAIQAV LSLYASGRTT GIVLDSGDGV T HNVPIYEG YALPHAIMRL DLAGRDLTDY LMKILTERGY SFVTTAEREI VRDIKEKLCY VALDFENEMA TAASSSSLEK SY ELPDGQV ITIGNERFRC PETLFQPSFI GMESAGIHET TYNSIMKCDI DIRKDLYANN VLSGGTTMYP GIADRMQKEI TAL APSTMK IKIIAPPERK YSVWIGGSIL ASLSTFQQMW ISKQEYDEAG PSIVHRKCF

-
Macromolecule #2: Myosin-binding protein C, cardiac-type

MacromoleculeName: Myosin-binding protein C, cardiac-type / type: protein_or_peptide / ID: 2
Details: only triple helix motif from C1-M construct bound to thin filament is visible in the map and contained in the model
Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.803123 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: DDPIGLFVMR PQDGEVTVGG SITFSARVAG ASLLKPPVVK WFKGKWVDLS SKVGQHLQLH DSYDRASKVY LFELHITDAQ PAFTGSYRC EVSTKDKFDC SNFNLTVHEA MGTGDLDLLS AFRRTSLAGG GRRISDSHED TGILDFSSLL KKRDSFRTPR D SKLEAPAE ...String:
DDPIGLFVMR PQDGEVTVGG SITFSARVAG ASLLKPPVVK WFKGKWVDLS SKVGQHLQLH DSYDRASKVY LFELHITDAQ PAFTGSYRC EVSTKDKFDC SNFNLTVHEA MGTGDLDLLS AFRRTSLAGG GRRISDSHED TGILDFSSLL KKRDSFRTPR D SKLEAPAE EDVWEILRQA PPSEYERIAF QYGVTDLRGM LKRLKGMRRD EKKSTAFQKK LE

-
Macromolecule #3: tropomyosin model

MacromoleculeName: tropomyosin model / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: pig (pig) / Organ: heart / Tissue: cardiac muscle
Molecular weightTheoretical: 11.507176 KDa
SequenceString: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) ...String:
(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statehelical array

-
Sample preparation

BufferpH: 7
GridModel: PELCO Ultrathin Carbon with Lacey Carbon / Material: COPPER / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 20 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 275 K / Instrument: FEI VITROBOT MARK IV

-
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: 3.5 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 34.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: OTHER / Details: F-actin model filtered to 100A resolution
Final angle assignmentType: NOT APPLICABLE / Software - Name: IHRSR
Final reconstructionApplied symmetry - Helical parameters - Δz: 27.4 Å
Applied symmetry - Helical parameters - Δ&Phi: -166.7 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 8.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: IHRSR / Number images used: 14282

-
Atomic model buiding 1

Initial model
PDB IDChain

chain_id: A

chain_id: A

chain_id: I
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-7tit:
Cardiac thin filament decorated with regulatory M-domain of cardiac myosin binding protein C

+
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