Structural evidence for variable oligomerization of the N-terminal domain of cyclase-associated protein (CAP).
Cyclase-associated protein (CAP) is a highly conserved and widely distributed protein that links the nutritional response signaling to cytoskeleton remodeling. In yeast, CAP is a component of the adenylyl cyclase complex and helps to activate the Ras-mediated catalytic cycle of the cyclase. While the N-terminal domain of CAP (N-CAP) provides a binding site for adenylyl cyclase, the C-terminal domain (C-CAP) possesses actin binding activity. Our attempts to crystallize full-length recombinant CAP from Dictyostelium discoideum resulted in growth of orthorhombic crystals containing only the N-terminal domain (residues 42-227) due to auto-proteolytic cleavage. The structure was solved by molecular replacement with data at 2.2 A resolution. The present crystal structure allows the characterization of a head-to-tail N-CAP dimer in the asymmetric unit and a crystallographic side-to-side dimer. Comparison with previously published structures of N-CAP reveals variable modes of dimerization of this domain, but the presence of a common interface for the side-to-side dimer.
Yusof
Adlina Mohd
AM
Institute of Structural & Molecular Biology, School of Biological Sciences, The University of Edinburgh, Scotland, United Kingdom.
Hu
Nien-Jen
NJ
Wlodawer
Alexander
A
Hofmann
Andreas
A
D000199:Actins / Q000737:chemistry; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D004023:Dictyostelium / Q000378:metabolism; D019281:Dimerization; D004798:Enzymes / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004798:Enzymes