6Z7U

Myosin-II motor domain complexed with blebbistatin in a new ADP-release conformation

6Z7U の概要

• エントリーDOI: 10.2210/pdb6z7u/pdb
• 分子名称: Myosin-2 heavy chain, 1,2-ETHANEDIOL, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: myosin, motorprotein, blebbistatin, adp-release, inhibitor, complex, hydrolase, motor protein
• 由来する生物種: Dictyostelium discoideum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 90002.31

構造登録者

Ewert, W.,Preller, M. (登録日: 2020-06-01, 公開日: 2020-10-21, 最終更新日: 2024-01-24)

主引用文献

Ewert, W.,Franz, P.,Tsiavaliaris, G.,Preller, M.
Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke.
Int J Mol Sci, 21:-, 2020

PubMed Abstract: The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.

PubMed: 33049993
DOI: 10.3390/ijms21197417

実験手法

X-RAY DIFFRACTION (2.58 Å)