2xns | pdb_00002xns
CRYSTAL STRUCTURE OF HUMAN G ALPHA I1 BOUND TO A DESIGNED HELICAL PEPTIDE DERIVED FROM THE GOLOCO MOTIF OF RGS14
Structural highlights
Function[GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[1] [2] [RGS14_HUMAN] Acts as a regulator of G protein signaling (RGS). Modulates G protein alpha subunits nucleotide exchange and hydrolysis activities by functioning either as a GTPase-activating protein (GAP), thereby driving G protein alpha subunits into their inactive GDP-bound form, or as a GDP-dissociation inhibitor (GDI). Confers GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not G(o) alpha subunit GNAO1 and G(i) alpha subunit GNAI2. Confers GAP activity on G(o) alpha subunit GNAI0 and G(i) alpha subunits GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS1 and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Probably required for the nerve growth factor (NGF)-mediated neurite outgrowth. May be involved in visual memory processing capacity and hippocampal-based learning and memory.[3] [4] Publication Abstract from PubMedThe de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to Galpha(i1). An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 A. Computational design of the sequence and structure of a protein-binding peptide.,Sammond DW, Bosch DE, Butterfoss GL, Purbeck C, Machius M, Siderovski DP, Kuhlman B J Am Chem Soc. 2011 Mar 30;133(12):4190-2. Epub 2011 Mar 9. PMID:21388199[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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