title: Structural characterization of a capping protein interaction motif defines a family of actin filament regulators.
abstract: Capping protein (CP) regulates actin dynamics by binding the barbed ends of actin filaments. Removal of CP may be one means to harness actin polymerization for processes such as cell movement and endocytosis. Here we structurally and biochemically investigated a CP interaction (CPI) motif present in the otherwise unrelated proteins CARMIL and CD2AP. The CPI motif wraps around the stalk of the mushroom-shaped CP at a site distant from the actin-binding interface, which lies on the top of the mushroom cap. We propose that the CPI motif may act as an allosteric modulator, restricting CP to a low-affinity, filament-binding conformation. Structure-based sequence alignments extend the CPI motif-containing family to include CIN85, CKIP-1, CapZIP and a relatively uncharacterized protein, WASHCAP (FAM21). Peptides comprising these CPI motifs are able to inhibit CP and to uncap CP-bound actin filaments.
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR, Proteos, Singapore.
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez-Valladares
authors.forename: Taekyung
authors.initials: T
authors.lastname: Kim
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Kannan
authors.forename: Alvin
authors.initials: A
authors.lastname: Tung
authors.forename: Adeleke H
authors.initials: AH
authors.lastname: Aguda
authors.forename: Mårten
authors.initials: M
authors.lastname: Larsson
authors.forename: John A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robinson
mesh_terms: D051344:Actin Capping Proteins / Q000737:chemistry* / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D051344:Actin Capping Proteins; D000199:Actins