|Entry||Database: PDB / ID: 7tj7|
|Title||Cardiac thin filament decorated with C1 Ig-domain and regulatory M-domain of cardiac myosin binding protein C (cMyBP-C)|
|Keywords||MOTOR PROTEIN / muscle contraction regulator / muscle protein|
|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 species||Homo sapiens (human)|
Sus scrofa (pig)
|Method||ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 8 Å|
|Authors||Risi, C.M. / Galkin, V.E.|
|Funding support|| United States, 2items |
|Citation||Journal: 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.
|Structure viewer||Molecule: |
Downloads & links
A: cardiac actin
B: cardiac actin
C: cardiac actin
D: cardiac actin
E: cardiac actin
F: cardiac actin
G: Myosin-binding protein C, cardiac-type
H: Myosin-binding protein C, cardiac-type
I: Myosin-binding protein C, cardiac-type
J: Myosin-binding protein C, cardiac-type
K: Myosin-binding protein C, cardiac-type
L: Myosin-binding protein C, cardiac-type
M: Myosin-binding protein C, cardiac-type
N: Myosin-binding protein C, cardiac-type
O: Myosin-binding protein C, cardiac-type
P: Myosin-binding protein C, cardiac-type
Q: Myosin-binding protein C, cardiac-type
R: Myosin-binding protein C, cardiac-type
S: tropomyosin model
T: tropomyosin model
U: tropomyosin model
V: tropomyosin model
Mass: 41830.551 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / Organ: heart / Tissue: cardiac muscle / References: UniProt: A0A4X1UMF3
Mass: 24803.123 Da / Num. of mol.: 12
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MYBPC3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q14896
Mass: 11507.176 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) / Organ: heart / Tissue: cardiac muscle
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: HELICAL ARRAY / 3D reconstruction method: helical reconstruction|
|Component||Name: Cardiac thin filament decorated with C1 Ig-domain and regulatory M-domain of cardiac myosin binding protein C (cMyBP-C)|
Details: Thin filaments decorated with C1-M fragment of cMyBP-C show bound triple helix motif of the M-domain and bound C1 Ig-domain.
Entity ID: all / Source: MULTIPLE SOURCES
|Molecular weight||Experimental value: NO|
|Buffer solution||pH: 7|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Specimen support||Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: PELCO Ultrathin Carbon with Lacey Carbon|
|Vitrification||Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 275 K|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3500 nm / Nominal defocus min: 1000 nm|
|Specimen holder||Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER|
|Image recording||Electron dose: 34 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)|
|Software||Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Helical symmerty||Angular rotation/subunit: -166.7 ° / Axial rise/subunit: 27.4 Å / Axial symmetry: C1|
|3D reconstruction||Resolution: 8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 9710 / Algorithm: BACK PROJECTION / Symmetry type: HELICAL|
|Atomic model building||Protocol: FLEXIBLE FIT / Space: REAL|
|Atomic model building|
|Refine LS restraints|
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