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Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

Abstract

The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central beta-sheet capped at each end by an alpha-helix. The presence of a four residue insertion in the region between beta-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a beta-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed.

Type Journal
ISBN 0925-2738 (Print)
Authors Ivancic, M.;Daly, R. J.;Lyons, B. A. :
Responsible Garvan Author
Publisher Name JOURNAL OF BIOMOLECULAR NMR
Published Date 2003-01-01
Published Volume 27
Published Issue 3
Published Pages 205-19
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12975581
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/1679