| http://purl.uniprot.org/citations/35177471 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35177471 | http://www.w3.org/2000/01/rdf-schema#comment | "In this study, we investigated the role of the super-relaxed (SRX) state of myosin in the structure-function relationship of sarcomeres in the hearts of mouse models of cardiomyopathy-bearing mutations in the human ventricular regulatory light chain (RLC, MYL2 gene). Skinned papillary muscles from hypertrophic (HCM-D166V) and dilated (DCM-D94A) cardiomyopathy models were subjected to small-angle X-ray diffraction simultaneously with isometric force measurements to obtain the interfilament lattice spacing and equatorial intensity ratios (I11/I10) together with the force-pCa relationship over a full range of [Ca2+] and at a sarcomere length of 2.1 μm. In parallel, we studied the effect of mutations on the ATP-dependent myosin energetic states. Compared with wild-type (WT) and DCM-D94A mice, HCM-D166V significantly increased the Ca2+ sensitivity of force and left shifted the I11/I10-pCa relationship, indicating an apparent movement of HCM-D166V cross-bridges closer to actin-containing thin filaments, thereby allowing for their premature Ca2+ activation. The HCM-D166V model also disrupted the SRX state and promoted an SRX-to-DRX (super-relaxed to disordered relaxed) transition that correlated with an HCM-linked phenotype of hypercontractility. While this dysregulation of SRX ↔ DRX equilibrium was consistent with repositioning of myosin motors closer to the thin filaments and with increased force-pCa dependence for HCM-D166V, the DCM-D94A model favored the energy-conserving SRX state, but the structure/function-pCa data were similar to WT. Our results suggest that the mutation-induced redistribution of myosin energetic states is one of the key mechanisms contributing to the development of complex clinical phenotypes associated with human HCM-D166V and DCM-D94A mutations."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2110328119"xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/author | "Ma W."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/author | "Liang J."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/author | "Yuan C.C."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/author | "Irving T.C."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/author | "Kazmierczak K."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/author | "Szczesna-Cordary D."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/pages | "e2110328119"xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/title | "Molecular basis of force-pCa relation in MYL2 cardiomyopathy mice: Role of the super-relaxed state of myosin."xsd:string |
| http://purl.uniprot.org/citations/35177471 | http://purl.uniprot.org/core/volume | "119"xsd:string |
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