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Locating an intramolecular binding site for the myristoylated N‐terminus of Galphai
Author(s) -
Preininger Anita M.,
Hamm Heidi E.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb23
Subject(s) - myristoylation , amino acid , gtp' , chemistry , cysteine , n terminus , binding site , protein structure , biochemistry , g protein , peptide sequence , biophysics , biology , signal transduction , phosphorylation , gene , enzyme
G‐protein α subunits transduce signals catalyzed by GPCRs to downstream effectors through GTP‐dependent conformational changes. In crystal structures, highly dynamic regions are often disordered. There are no current structures resolving the myristoylated amino terminus of Gα proteins, therefore we have applied biophysical measures in the study of amino terminal structure and function. In this system we have examined a series of cysteine mutations throughout the amino terminus of Gα il proteins in a background lacking solvent exposed cysteines. We have previously demonstrated that amino terminal residues in a myristoylated Gα protein are more immobilized and solvent excluded than their non‐myristoylated counterparts, even in the absence of Gβγ, suggesting an intramolecular binding site for the myristoylated amino terminus of Gα i proteins (Biochemistry, 2003, 42: 7931). In this work we describe myristoylation‐dependent differences in environments of the bound nucleotide and residues in the Switch II region and implications for an intramolecular binding site for the amino terminus, as revealed by biophysical investigations of G‐protein structure and function. Together these studies provide key insights into conformational changes that occur dynamically in solution during G‐protein signaling.