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PMID: 20357771 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structural characterization of a capping protein interaction motif defines a family of actin filament regulators.

Nature structural & molecular biology ·Vol. 17 ·No. 4 ·2010-04-00 ·Pages 497-503

Hernandez-Valladares M, Kim T, Kannan B, Tung A, Aguda AH, Larsson M, Cooper JA, Robinson RC

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.

MeSH Terms
Actin Capping Proteins/chemistry,metabolism Actins/metabolism Amino Acid Sequence Models, Molecular Molecular Sequence Data Protein Conformation Sequence Homology, Amino Acid
Chemicals
Actin Capping Proteins Actins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Hernandez-Valladares Maria
Institute of Molecular and Cell Biology, A*STAR, Proteos, Singapore.
Kim Taekyung
Kannan Balakrishnan
Tung Alvin
Aguda Adeleke H
Larsson Mårten
Cooper John A
Robinson Robert C
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1792
Published
2010-04-00
Epub
2010-00-28
Pages
497-503
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3150215
Subset
IM
Grants
NIGMS NIH HHS · R01 GM038542 · United States
NIGMS NIH HHS · R01 GM038542-22A1 · United States
Databases
PDB
3LK2, 3LK3, 3LK4
External Links
PubMed source DOI: 10.1038/nsmb.1792 PMC Full Text View journal details
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