title: Role of the actin Ala-108-Pro-112 loop in actin polymerization and ATPase activities.
abstract: Actin plays fundamental roles in a variety of cell functions in eukaryotic cells. The polymerization-depolymerization cycle, between monomeric G-actin and fibrous F-actin, drives essential cell processes. Recently, we proposed the atomic model for the F-actin structure and found that actin was in the twisted form in the monomer and in the untwisted form in the filament. To understand how the polymerization process is regulated (Caspar, D. L. (1991) Curr. Biol. 1, 30-32), we need to know further details about the transition from the twisted to the untwisted form. For this purpose, we focused our attention on the Ala-108-Pro-112 loop, which must play crucial roles in the transition, and analyzed the consequences of the amino acid replacements on the polymerization process. As compared with the wild type, the polymerization of P109A was accelerated in both the nucleation and the elongation steps, and this was attributed to an increase in the frequency factor of the Arrhenius equation. The multiple conformations allowed by the substitution presumably resulted in the effective formation of the collision complex, thus accelerating polymerization. On the other hand, the A108G mutation reduced the rates of both nucleation and elongation due to an increase in the activation energy. In the cases of polymerization acceleration and deceleration, each functional aberration is attributed to a distinct elementary process. The rigidity of the loop, which mediates neither too strong nor too weak interactions between subdomains 1 and 3, might play crucial roles in actin polymerization.
authors.affiliation: ERATO Actin Filament Dynamics Project, Japan Science and Technology Agency, c/o RIKEN SPring-8 Center, Kouto 1-1, Sayo, Hyogo 679-5148, Japan.
authors.forename: Mitsusada
authors.initials: M
authors.lastname: Iwasa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Aihara
authors.forename: Kayo
authors.initials: K
authors.lastname: Maeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Narita
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maéda
authors.forename: Toshiro
authors.initials: T
authors.lastname: Oda
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D006801:Humans; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000199:Actins; D030161:Avian Proteins; D009097:Multienzyme Complexes; D000251:Adenosine Triphosphatases