Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites / genetics
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Crystallography, X-Ray
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GTP-Binding Proteins / metabolism*
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Humans
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Molecular Sequence Data
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor) / chemistry*
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Protein Folding
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Sequence Alignment
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Signal Transduction
Substances
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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GTP-Binding Proteins
Associated data
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GENBANK/D31962
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GENBANK/M94721
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GENBANK/P11274
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GENBANK/P15882
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GENBANK/P23726
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GENBANK/P23727
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GENBANK/P26450
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GENBANK/P27986
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GENBANK/P30337
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GENBANK/P32019
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GENBANK/P32873
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GENBANK/P38339
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GENBANK/P39083
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GENBANK/P39960
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GENBANK/P40809
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GENBANK/Q01968
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GENBANK/Q03070
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GENBANK/U01147
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GENBANK/U02289
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GENBANK/X78817
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GENBANK/X87671
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GENBANK/Z23024