title: A novel actin binding site of myosin required for effective muscle contraction.
abstract: F-actin serves as a track for myosin's motor functions and activates its ATPase activity by several orders of magnitude, enabling actomyosin to produce effective force against load. Although actin activation is a ubiquitous property of all myosin isoforms, the molecular mechanism and physiological role of this activation are unclear. Here we describe a conserved actin-binding region of myosin named the 'activation loop', which interacts with the N-terminal segment of actin. We demonstrate by biochemical, biophysical and in vivo approaches using transgenic Caenorhabditis elegans strains that the interaction between the activation loop and actin accelerates the movement of the relay, stimulating myosin's ATPase activity. This interaction results in efficient force generation, but it is not essential for the unloaded motility. We conclude that the binding of actin to myosin's activation loop specifically increases the ratio of mechanically productive to futile myosin heads, leading to efficient muscle contraction.
authors.affiliation: Department of Biochemistry, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Boglárka H
authors.initials: BH
authors.lastname: Várkuti
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Yang
authors.forename: Bálint
authors.initials: B
authors.lastname: Kintses
authors.forename: Péter
authors.initials: P
authors.lastname: Erdélyi
authors.forename: Irén
authors.initials: I
authors.lastname: Bárdos-Nagy
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
authors.forename: Péter
authors.initials: P
authors.lastname: Hári
authors.forename: Miklós
authors.initials: M
authors.lastname: Kellermayer
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
authors.forename: András
authors.initials: A
authors.lastname: Málnási-Csizmadia
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000378:metabolism; D004023:Dictyostelium / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009119:Muscle Contraction; D009154:Mutation; D009218:Myosins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary
chemical_list: D000199:Actins; D009218:Myosins