6FSA

Beta-Cardiac myosin post-rigor

6FSA の概要

• エントリーDOI: 10.2210/pdb6fsa/pdb
• 分子名称: Myosin-7, Myosin light chain 3, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: motor protein, myosin, hypertrophic cardiomyopathy
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 492405.54

構造登録者

Robert-Paganin, J.,Auguin, D.,Houdusse, A. (登録日: 2018-02-19, 公開日: 2018-07-25, 最終更新日: 2024-01-17)

主引用文献

Robert-Paganin, J.,Auguin, D.,Houdusse, A.
Hypertrophic cardiomyopathy disease results from disparate impairments of cardiac myosin function and auto-inhibition.
Nat Commun, 9:4019-4019, 2018

PubMed Abstract: Hypertrophic cardiomyopathies (HCM) result from distinct single-point mutations in sarcomeric proteins that lead to muscle hypercontractility. While different models account for a pathological increase in the power output, clear understanding of the molecular basis of dysfunction in HCM is the mandatory next step to improve current treatments. Here, we present an optimized quasi-atomic model of the sequestered state of cardiac myosin coupled to X-ray crystallography and in silico analysis of the mechanical compliance of the lever arm, allowing the systematic study of a large set of HCM mutations and the definition of different mutation classes based on their effects on lever arm compliance, sequestered state stability, and motor functions. The present work reconciles previous models and explains how distinct HCM mutations can have disparate effects on the motor mechano-chemical parameters and yet lead to the same disease. The framework presented here can guide future investigations aiming at finding HCM treatments.

PubMed: 30275503
DOI: 10.1038/s41467-018-06191-4

実験手法

X-RAY DIFFRACTION (2.33 Å)