1xhm | pdb_00001xhm
The Crystal Structure of a Biologically Active Peptide (SIGK) Bound to a G Protein Beta:Gamma Heterodimer
Structural highlights
Function[GBB1_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [GBG2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedG protein betagamma subunits associate with many binding partners in cellular signaling cascades. In previous work, we used random-peptide phage display screening to identify a diverse family of peptides that bound to a common surface on Gbetagamma subunits and blocked a subset of Gbetagamma effectors. Later studies showed that one of the peptides caused G protein activation through a novel Gbetagamma-dependent, nucleotide exchange-independent mechanism. Here we report the X-ray crystal structure of Gbeta(1)gamma(2) bound to this peptide, SIGK (SIGKAFKILGYPDYD), at 2.7 A resolution. SIGK forms a helical structure that binds the same face of Gbeta(1) as the switch II region of Galpha. The interaction interface can be subdivided into polar and nonpolar interfaces that together contain a mixture of binding determinants that may be responsible for the ability of this surface to recognize multiple protein partners. Systematic mutagenic analysis of the peptide-Gbeta(1) interface indicates that distinct sets of amino acids within this interface are required for binding of different peptides. Among these unique amino acid interactions, specific electrostatic binding contacts within the polar interface are required for peptide-mediated subunit dissociation. The data provide a mechanistic basis for multiple target recognition by Gbetagamma subunits with diverse functional interactions within a common interface and suggest that pharmacological targeting of distinct regions within this interface could allow for selective manipulation of Gbetagamma-dependent signaling pathways. Structural and molecular characterization of a preferred protein interaction surface on G protein beta gamma subunits.,Davis TL, Bonacci TM, Sprang SR, Smrcka AV Biochemistry. 2005 Aug 9;44(31):10593-604. PMID:16060668[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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