Mapping the phosphoinositide-binding site on chick cofilin explains how PIP2 regulates the cofilin-actin interaction.
Cofilin plays a key role in the choreography of actin dynamics via its ability to sever actin filaments and increase the rate of monomer dissociation from pointed ends. The exact manner by which phosphoinositides bind to cofilin and inhibit its interaction with actin has proven difficult to ascertain. We determined the structure of chick cofilin and used NMR chemical shift mapping and structure-directed mutagenesis to unambiguously locate its recognition site for phosphoinositides (PIs). This structurally unique recognition site requires both the acyl chain and head group of the PI for a productive interaction, and it is not inhibited by phosphorylation of cofilin. We propose that the interaction of cofilin with membrane-bound PIs abrogates its binding to both actin and actin-interacting protein 1, and facilitates spatiotemporal regulation of cofilin activity.
Gorbatyuk
Vitaliy Y
VY
Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
Nosworthy
Neil J
NJ
Robson
Scott A
SA
Bains
Naresh P S
NP
Maciejewski
Mark W
MW
Dos Remedios
Cris G
CG
King
Glenn F
GF
D051339:Actin Depolymerizing Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002642:Chick Embryo; D002874:Chromosome Mapping; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry / Q000502:physiology*; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D016415:Sequence Alignment
D051339:Actin Depolymerizing Factors; D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols