1XHM

The Crystal Structure of a Biologically Active Peptide (SIGK) Bound to a G Protein Beta:Gamma Heterodimer

1XHM の概要

• エントリーDOI: 10.2210/pdb1xhm/pdb
• 関連するPDBエントリー: 1A0R 1GG2 1OMW 1TBG
• 分子名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit, SIGK Peptide, ... (4 entities in total)
• 機能のキーワード: wd40 repeat, beta-propeller, protein-peptide complex, signaling protein
• 由来する生物種: Bos taurus (cattle); 詳細
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P63212
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 47795.87

構造登録者

Davis, T.L.,Bonacci, T.M.,Smrcka, A.V.,Sprang, S.R. (登録日: 2004-09-20, 公開日: 2005-08-09, 最終更新日: 2023-08-23)

主引用文献

Davis, T.L.,Bonacci, T.M.,Sprang, S.R.,Smrcka, A.V.
Structural and Molecular Characterization of a Preferred Protein Interaction Surface on G Protein betagamma Subunits.
Biochemistry, 44:10593-10604, 2005

PubMed Abstract: G 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.

PubMed: 16060668
DOI: 10.1021/bi050655i

実験手法

X-RAY DIFFRACTION (2.7 Å)