title: Inorganic phosphate regulates the binding of cofilin to actin filaments.
abstract: Inorganic phosphate (Pi) and cofilin/actin depolymerizing factor proteins have opposite effects on actin filament structure and dynamics. Pi stabilizes the subdomain 2 in F-actin and decreases the critical concentration for actin polymerization. Conversely, cofilin enhances disorder in subdomain 2, increases the critical concentration, and accelerates actin treadmilling. Here, we report that Pi inhibits the rate, but not the extent of cofilin binding to actin filaments. This inhibition is also significant at physiological concentrations of Pi, and more pronounced at low pH. Cofilin prevents conformational changes in F-actin induced by Pi, even at high Pi concentrations, probably because allosteric changes in the nucleotide cleft decrease the affinity of Pi to F-actin. Cofilin induced allosteric changes in the nucleotide cleft of F-actin are also indicated by an increase in fluorescence emission and a decrease in the accessibility of etheno-ADP to collisional quenchers. These changes transform the nucleotide cleft of F-actin to G-actin-like. Pi regulation of cofilin binding and the cofilin regulation of Pi binding to F-actin can be important aspects of actin based cell motility.
authors.affiliation: Institute of Dental Sciences, School of Dental Medicine, Hebrew University of Jerusalem, Israel. muhlrad@cc.huji.ac.il
authors.forename: Andras
authors.initials: A
authors.lastname: Muhlrad
authors.forename: Dmitry
authors.initials: D
authors.lastname: Pavlov
authors.forename: Y Michael
authors.initials: YM
authors.lastname: Peyser
authors.forename: Emil
authors.initials: E
authors.lastname: Reisler
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D010710:Phosphates / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020860:Subtilisin / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D010710:Phosphates; D020860:Subtilisin