title: ATPase activity and conformational changes in the regulation of actin.
abstract: The eukaryotic microfilament system is regulated in part through the nucleotide- and cation-dependent conformation of the actin molecule. In this review, recent literature on the crystal and solution structures of actin and other actin-superfamily proteins is summarized. Furthermore, the structure of the nucleotide binding cleft is discussed in terms of the mechanism of ATP hydrolysis and P(i) release. Two distinct domain movements are suggested to participate in the regulation of actin. (1) High-affinity binding of Mg(2+) to actin induces a rearrangement of side chains in the nucleotide binding site leading to an increased ATPase activity and polymerizability, as well as a rotation of subdomain 2 which is mediated by the hydroxyl of serine-14. (2) Hydrolysis of ATP and subsequent release of inorganic phosphate lead to a butterfly-like opening of the actin molecule brought about by a shearing in the interdomain helix 135-150. These domain rearrangements modulate the interaction of actin with a variety of different proteins, and conversely, protein binding to actin can restrict these conformational changes, with ultimate effects on the assembly state of the microfilament system.
authors.affiliation: Department of Cell Biology, Wenner-Gren Institute, Stockholm University, S-106 91, Stockholm, Sweden. schulh01@med.nyu.edu
authors.forename: H
authors.initials: H
authors.lastname: Schüler
mesh_terms: D000199:Actins / Q000737:chemistry*; D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D008958:Models, Molecular; D009218:Myosins / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D000199:Actins; D010710:Phosphates; D012996:Solutions; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D009218:Myosins