title: A change in actin conformation associated with filament instability after Pi release.
abstract: The ability of actin to both polymerize into filaments and to depolymerize permits the rapid rearrangements of actin structures that are essential for actin's function in most cellular processes. Filament polarity and dynamic properties are conferred by the hydrolysis of ATP on actin filaments. Release of inorganic phosphate (Pi) from filaments after ATP hydrolysis promotes depolymerization. We identify a yeast actin mutation, Val-159 to Asn, which uncouples Pi release from the conformational change that results in filament destabilization. Three-dimensional reconstructions of electron micrographs reveal a conformational difference between ADP-Pi filaments and ADP filaments and show that ADP V159N filaments resemble ADP-Pi wild-type filaments. Crystal structures of mammalian beta-actin in which the nucleotide binding cleft is in the "open" and "closed" states can be used to model actin filaments in the ADP and ADP-Pi conformations, respectively. We propose that these two conformations of G-actin may be related to two functional states of F-actin.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720-3202, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Belmont
authors.forename: A
authors.initials: A
authors.lastname: Orlova
authors.forename: D G
authors.initials: DG
authors.lastname: Drubin
authors.forename: E H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001608:Beryllium / Q000378:metabolism; D020134:Catalytic Domain; D005459:Fluorides / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D009154:Mutation; D010710:Phosphates / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D014633:Valine
chemical_list: D000199:Actins; D010710:Phosphates; D011994:Recombinant Proteins; C035982:beryllium fluoride; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014633:Valine; D001608:Beryllium; D005459:Fluorides