Crystal structure of the actin binding domain of the cyclase-associated protein.
Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed beta-helix flanked by antiparallel beta-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface. This structural and biochemical characterization provides new insights into the organization and potential mechanistic properties of the multiprotein assemblies that integrate dynamic actin processes into the overall physiology of the cell. An unanticipated finding is that the unique tertiary structure of the C-CAP monomer provides a structural model for a wide range of molecules, including RP2 and cofactor C, proteins involved in X-linked retinitis pigmentosa and tubulin maturation, respectively, as well as several uncharacterized proteins that exhibit very diverse domain organizations. Thus, the unusual right-handed beta-helical fold present in C-CAP appears to support a wide range of biological functions.
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Tetyana
T
Dodatko
Alexander A
AA
Fedorov
Marcin
M
Grynberg
Yury
Y
Patskovsky
Denise A
DA
Rozwarski
Lukasz
L
Jaroszewski
Eliah
E
Aronoff-Spencer
Elena
E
Kondraskina
Tom
T
Irving
Adam
A
Godzik
Steven C
SC
Almo
D000199:Actins / Q000737:chemistry*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D040681:Structural Homology, Protein
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C073751:SRV2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins