1fyr

From Proteopedia

Revision as of 10:44, 21 February 2008

DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX

Overview

Src homology 2 (SH2) domains are key modules in intracellular signal transduction. They link activated cell surface receptors to downstream targets by binding to phosphotyrosine-containing sequence motifs. The crystal structure of a Grb2-SH2 domain-phosphopeptide complex was determined at 2.4 A resolution. The asymmetric unit contains four polypeptide chains. There is an unexpected domain swap so that individual chains do not adopt a closed SH2 fold. Instead, reorganization of the EF loop leads to an open, nonglobular fold, which associates with an equivalent partner to generate an intertwined dimer. As in previously reported crystal structures of canonical Grb2-SH2 domain-peptide complexes, each of the four hybrid SH2 domains in the two domain-swapped dimers binds the phosphopeptide in a type I beta-turn conformation. This report is the first to describe domain swapping for an SH2 domain. While in vivo evidence of dimerization of Grb2 exists, our SH2 dimer is metastable and a physiological role of this new form of dimer formation remains to be demonstrated.

Disease

Known diseases associated with this structure: Autism, suseptibility to, 9 OMIM:[164860], Central hypoventilation syndrome, congenital OMIM:[100790], Haddad syndrome OMIM:[100790], Hepatocellular carcinoma, childhood type OMIM:[164860], Renal cell carcinoma, papillary, familial and sporadic OMIM:[164860]

About this Structure

1FYR is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex., Schiering N, Casale E, Caccia P, Giordano P, Battistini C, Biochemistry. 2000 Nov 7;39(44):13376-82. PMID:11063574

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