Musacchio A, Cantley L C, Harrison S C
Laboratory of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14373-8. doi: 10.1073/pnas.93.25.14373.
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.
诸如断裂点簇集区产物、嵌合蛋白以及Src同源3结合蛋白3BP1等蛋白质，是小GTP结合蛋白（G蛋白或GTP酶）Rho亚家族成员的GTP酶激活蛋白（GAP）。一个由200个氨基酸残基组成的区域，命名为断裂点簇集区同源（BH）结构域，负责GAP活性。我们在此描述了磷脂酰肌醇3激酶p85亚基的BH结构域在2.0埃分辨率下的晶体结构。该结构域由七个螺旋组成，呈一种此前未观察到的排列方式。由四个螺旋组成的核心包含了BH家族中大多数保守的残基。它们的堆积方式暗示了一个G蛋白结合位点的位置。这种小GTP结合蛋白的类GAP结构域的结构为分析这类分子的功能提供了一个框架。
