6DUE

Toxoplasma gondii MyoA, a Class-XIV myosin, in the pre-powerstroke state

6DUE の概要

• エントリーDOI: 10.2210/pdb6due/pdb
• 分子名称: Myosin A, ADENOSINE-5'-DIPHOSPHATE, TETRAFLUOROALUMINATE ION, ... (6 entities in total)
• 機能のキーワード: apicomplexan, myosin, atpase, motor protein
• 由来する生物種: Toxoplasma gondii (strain ATCC 50853 / GT1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 89129.16

構造登録者

Powell, C.J.,Boulanger, M.J. (登録日: 2018-06-20, 公開日: 2018-10-31, 最終更新日: 2023-10-11)

主引用文献

Powell, C.J.,Ramaswamy, R.,Kelsen, A.,Hamelin, D.J.,Warshaw, D.M.,Bosch, J.,Burke, J.E.,Ward, G.E.,Boulanger, M.J.
Structural and mechanistic insights into the function of the unconventional class XIV myosin MyoA fromToxoplasma gondii.
Proc. Natl. Acad. Sci. U.S.A., 115:E10548-E10555, 2018

PubMed Abstract: Parasites of the phylum Apicomplexa are responsible for significant morbidity and mortality on a global scale. Central to the virulence of these pathogens are the phylum-specific, unconventional class XIV myosins that power the essential processes of parasite motility and host cell invasion. Notably, class XIV myosins differ from human myosins in key functional regions, yet they are capable of fast movement along actin filaments with kinetics rivaling previously studied myosins. Toward establishing a detailed molecular mechanism of class XIV motility, we determined the 2.6-Å resolution crystal structure of the MyoA (TgMyoA) motor domain. Structural analysis reveals intriguing strategies for force transduction and chemomechanical coupling that rely on a divergent SH1/SH2 region, the class-defining "HYAG"-site polymorphism, and the actin-binding surface. In vitro motility assays and hydrogen-deuterium exchange coupled with MS further reveal the mechanistic underpinnings of phosphorylation-dependent modulation of TgMyoA motility whereby localized regions of increased stability and order correlate with enhanced motility. Analysis of solvent-accessible pockets reveals striking differences between apicomplexan class XIV and human myosins. Extending these analyses to high-confidence homology models of and MyoA motor domains supports the intriguing potential of designing class-specific, yet broadly active, apicomplexan myosin inhibitors. The successful expression of the functional TgMyoA complex combined with our crystal structure of the motor domain provides a strong foundation in support of detailed structure-function studies and enables the development of small-molecule inhibitors targeting these devastating global pathogens.

PubMed: 30348763
DOI: 10.1073/pnas.1811167115

実験手法

X-RAY DIFFRACTION (2.6 Å)