Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit.
Proteins such as the product of the break-point cluster region, chimaerin, and the Src homology 3-binding protein 3BP1, are GTPase activating proteins (GAPs) for members of the Rho subfamily of small GTP-binding proteins (G proteins or GTPases). A 200-residue region, named the breakpoint cluster region-homology (BH) domain, is responsible for the GAP activity. We describe here the crystal structure of the BH domain from the p85 subunit of phosphatidylinositol 3-kinase at 2.0 A resolution. The domain is composed of seven helices, having a previously unobserved arrangement. A core of four helices contains most residues that are conserved in the BH family. Their packing suggests the location of a G-protein binding site. This structure of a GAP-like domain for small GTP-binding proteins provides a framework for analyzing the function of this class of molecules.
Musacchio
A
A
Laboratory of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.
Cantley
L C
LC
Harrison
S C
SC
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D016415:Sequence Alignment; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019204:GTP-Binding Proteins