title: Role of insert-1 of myosin VI in modulating nucleotide affinity.
abstract: 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.
authors.affiliation: Structural Motility, Institut Curie CNRS, UMR144, Paris, France.
authors.forename: Olena
authors.initials: O
authors.lastname: Pylypenko
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.forename: Gaelle
authors.initials: G
authors.lastname: Squires
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zong
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D006801:Humans; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: C089785:myosin VI; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D018995:Myosin Heavy Chains