Mammalian and Malaria Parasite Cyclase-associated Proteins Catalyze Nucleotide Exchange on G-actin through a Conserved Mechanism
Details
Publication Year 2013-01-11,Volume 288,Issue #2,Page 984-994
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
Publication Type
Journal Article
Abstract
Cyclase-associated proteins (CAPs) are among the most highly conserved regulators of actin dynamics, being present in organisms from mammals to apicomplexan parasites. Yeast, plant, and mammalian CAPs are large multidomain proteins, which catalyze nucleotide exchange on actin monomers from ADP to ATP and recycle actin monomers from actin-depolymerizing factor (ADF)/cofilin for new rounds of filament assembly. However, the mechanism by which CAPs promote nucleotide exchange is not known. Furthermore, how apicomplexan CAPs, which lack many domains present in yeast and mammalian CAPs, contribute to actin dynamics is not understood. We show that, like yeast Srv2/CAP, mouse CAP1 interacts with ADF/cofilin and ADP-G-actin through its N-terminal alpha-helical and C-terminal beta-strand domains, respectively. However, in the variation to yeast Srv2/CAP, mouse CAP1 has two adjacent profilin-binding sites, and it interacts with ATP-actin monomers with high affinity through its WH2 domain. Importantly, we revealed that the C-terminal beta-sheet domain of mouse CAP1 is essential and sufficient for catalyzing nucleotide exchange on actin monomers, although the adjacent WH2 domain is not required for this function. Supporting these data, we show that the malaria parasite Plasmodium falciparum CAP, which is entirely composed of the beta-sheet domain, efficiently promotes nucleotide exchange on actin monomers. Collectively, this study provides evidence that catalyzing nucleotide exchange on actin monomers via the beta-sheet domain is the most highly conserved function of CAPs from mammals to apicomplexan parasites. Other functions, including interactions with profilin and ADF/cofilin, evolved in more complex organisms to adjust the specific role of CAPs in actin dynamics.
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords
DEPOLYMERIZING FACTOR; FILAMENT TURNOVER; IN-VIVO; SRV2/CAP COMPLEX; REGULATES ACTIN; NONMUSCLE CELLS; WH2 DOMAIN; ATP-ACTIN; ADP-ACTIN; PROFILIN
Research Division(s)
Infection And Immunity
Terms of Use/Rights Notice
© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.


Creation Date: 2013-01-11 12:00:00
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