TY - JOUR
T1 - Structural characterization of a capping protein interaction motif defines a family of actin filament regulators
AU - Hernandez-Valladares, Maria
AU - Kim, Taekyung
AU - Kannan, Balakrishnan
AU - Tung, Alvin
AU - Aguda, Adeleke H.
AU - Larsson, Mrten
AU - Cooper, John A.
AU - Robinson, Robert C.
N1 - Funding Information:
We thank the Biomedical Research Council of A*STAR for support to R.C.R. and the National Synchrotron Radiation Research Center, a facility supported by the National Science Council of Taiwan for provision of beam time and assistance in data collection. The Synchrotron Radiation Protein Crystallography Facility is supported by the National Research Program for Genomic Medicine. J.A.C. acknowledges US National Institutes of Health grant GM 38542 for support.
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77950500990&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1792
DO - 10.1038/nsmb.1792
M3 - Article
C2 - 20357771
AN - SCOPUS:77950500990
SN - 1545-9993
VL - 17
SP - 497
EP - 503
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 4
ER -