View source for 7tj7


==Cardiac thin filament decorated with C1 Ig-domain and regulatory M-domain of cardiac myosin binding protein C (cMyBP-C)==
<StructureSection load='7tj7' size='340' side='right'caption='[[7tj7]], [[Resolution|resolution]] 8.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tj7]] is a 22 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TJ7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 8&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tj7 OCA], [https://pdbe.org/7tj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tj7 RCSB], [https://www.ebi.ac.uk/pdbsum/7tj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tj7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACTS_PIG ACTS_PIG] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
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== Publication Abstract from PubMed ==
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(2+) 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.

Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.,Risi CM, Villanueva E, Belknap B, Sadler RL, Harris SP, White HD, Galkin VE J Mol Biol. 2022 Dec 30;434(24):167879. doi: 10.1016/j.jmb.2022.167879. Epub 2022 , Nov 10. PMID:36370805<ref>PMID:36370805</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7tj7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tropomyosin 3D structures|Tropomyosin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Galkin VE]]
[[Category: Risi CM]]