Force-producing ADP state of myosin bound to actin

• Verfasst von: Wulf, Sarah Elise Freyja [VerfasserIn]
• Verfasst von: Ropars, Virginie [VerfasserIn]
• Verfasst von: Fujita-Becker, Setsuko [VerfasserIn]
• Verfasst von: Oster, Marco [VerfasserIn]
• Verfasst von: Hofhaus, Götz [VerfasserIn]
• Verfasst von: Trabuco, Leonardo G. [VerfasserIn]
• Verfasst von: Pylypenko, Olena [VerfasserIn]
• Verfasst von: Sweeney, H. Lee [VerfasserIn]
• Verfasst von: Houdusse, Anne M. [VerfasserIn]
• Verfasst von: Schröder, Rasmus R. [VerfasserIn]
• Titel: Force-producing ADP state of myosin bound to actin
• Verf.angabe: Sarah F. Wulf, Virginie Ropars, Setsuko Fujita-Becker, Marco Oster, Goetz Hofhaus, Leonardo G. Trabuco, Olena Pylypenko, H. Lee Sweeney, Anne M. Houdusse, and Rasmus R. Schröder
• E-Jahr: 2016
• Jahr: March 14, 2016
• Umfang: 9 S.
• Fussnoten: Gesehen am 18.02.2020
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2016
• Band/Heft Quelle: 113(2016), 13, Seite E1844-E1852
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1516598113
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: force generation
• Sach-SW: molecular motor
• Sach-SW: myosin V
• Sach-SW: transducer
• K10plus-PPN: 1690220864

Abstract

Molecular motors produce force when they interact with their cellular tracks. For myosin motors, the primary force-generating state has MgADP tightly bound, whereas myosin is strongly bound to actin. We have generated an 8-Å cryoEM reconstruction of this state for myosin V and used molecular dynamics flexed fitting for model building. We compare this state to the subsequent state on actin (Rigor). The ADP-bound structure reveals that the actin-binding cleft is closed, even though MgADP is tightly bound. This state is accomplished by a previously unseen conformation of the β-sheet underlying the nucleotide pocket. The transition from the force-generating ADP state to Rigor requires a 9.5° rotation of the myosin lever arm, coupled to a β-sheet rearrangement. Thus, the structure reveals the detailed rearrangements underlying myosin force generation as well as the basis of strain-dependent ADP release that is essential for processive myosins, such as myosin V.