Structural insights into the intertwined dimer of fyn SH2.

TitleStructural insights into the intertwined dimer of fyn SH2.
Publication TypeJournal Article
Year of Publication2015
AuthorsHuculeci, R., A. Garcia-Pino, L. Buts, T. Lenaerts, and N. van Nuland
JournalProtein Sci
Volume24
Issue12
Pagination1964-78
Date Published2015 Dec
ISSN1469-896X
KeywordsCrystallography, X-Ray, Humans, Models, Molecular, Peptides, Phosphotyrosine, Protein Multimerization, Protein Structure, Secondary, Proto-Oncogene Proteins c-fyn, src Homology Domains
Abstract

Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand.

DOI10.1002/pro.2806
Alternate JournalProtein Sci.
PubMed ID26384592
PubMed Central IDPMC4815226
Research group: