Role of Insert-1 of Myosin VI in Modulating Nucleotide Affinity

Olena Pylypenko (1) , Lin Song (2) , Gaelle Squires (3) , Xiaoyan Liu (2) , Alan B Zong (2) , Anne Houdusse (1) , H Lee Sweeney (2)

1 Biologie Cellulaire et Cancer
2 University of Pennsylvania School of Veterinary Medicine
3 CDC - Compartimentation et dynamique cellulaires

Myosin VI is unique in its directionality among myosin superfamily members and also displays a slow and strain-dependent rate of ATP binding that allows for gating between its heads. In this study we demonstrate that leucine 310 is positioned by a class VI-specific insert, insert-1, so as to account for the selective hindrance of ATP versus ADP binding. Mutation of leucine 310 to glycine removes all influence of insert-1 on ATP binding. Furthermore, by analyzing myosin VI structures with either leucine 310 substituted to a glycine or complete removal of insert-1, we conclude that nucleotides may initially bind to myosin by their purine rings before docking their phosphate moieties. Otherwise, insert-1 could not exert a differential influence on ATP versus ADP binding.

Domaines: Biologie structurale [q-bio.BM]

Olena Pylypenko, Lin Song, Gaelle Squires, Xiaoyan Liu, Alan B Zong, et al.. Role of Insert-1 of Myosin VI in Modulating Nucleotide Affinity. Journal of Biological Chemistry, 2011, 286 (13), pp.11716 - 11723. ⟨10.1074/jbc.m110.200626⟩. ⟨hal-03059381⟩