title: Remote changes in the dynamics of the phosphotyrosine-binding domain of insulin receptor substrate-1 induced by phosphopeptide binding.
abstract: Protein structures consist of cooperative networks of interactions that can extend substantial distances across the protein structure and have significant consequences for stability and function. To characterize such interaction networks within the phosphotyrosine-binding domain of insulin receptor substrate-1 (IRS-PTB), we have used NMR relaxation to determine the dynamics of backbone amide groups, side chain methyl groups, and tryptophan side chain indole groups in IRS-PTB, both in the absence and in the presence of a bound phosphotyrosine-containing peptide. Although there are minimal differences between the structures of apo and peptide-bound forms, primarily localized close to the peptide binding site, we observe significant changes in dynamics for residues located remotely from the binding site. These residues are clustered together and appear to constitute a network of interactions that is coupled to the peptide binding site through intervening residues.
authors.affiliation: Department of Chemistry and Interdisciplinary Biochemistry Program, Indiana University, Bloomington, Indiana 47405-0001, USA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Jarymowycz
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stone
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D019000:Phosphotyrosine / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010748:Phosphopeptides; D019000:Phosphotyrosine