title: Structural insights into the intertwined dimer of fyn SH2.
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.
authors.affiliation: Structural Biology Brussels, Jean Jeener NMR Center, Vrije Universiteit Brussel, Brussels, Belgium.|Structural Biology Research Center, VIB, Brussels, Belgium.
authors.forename: Radu
authors.initials: R
authors.lastname: Huculeci
authors.affiliation: Structural Biology Brussels, Jean Jeener NMR Center, Vrije Universiteit Brussel, Brussels, Belgium.|Structural Biology Research Center, VIB, Brussels, Belgium.
authors.forename: Abel
authors.initials: A
authors.lastname: Garcia-Pino
authors.affiliation: Structural Biology Brussels, Jean Jeener NMR Center, Vrije Universiteit Brussel, Brussels, Belgium.|Structural Biology Research Center, VIB, Brussels, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Buts
authors.affiliation: MLG, Département d'Informatique, Université Libre de Bruxelles, Brussels, Belgium.|AI-Lab,Vakgroep Computerwetenschappen, Vrije Universiteit Brussel, Brussels, Belgium.|Interuniversity Institute of Bioinformatics Brussels (IB2), ULB-VUB, Brussels, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Lenaerts
authors.affiliation: Structural Biology Brussels, Jean Jeener NMR Center, Vrije Universiteit Brussel, Brussels, Belgium.|Structural Biology Research Center, VIB, Brussels, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: van Nuland
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D051076:Proto-Oncogene Proteins c-fyn / Q000737:chemistry* / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D010455:Peptides; D019000:Phosphotyrosine; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn
keywords: Fyn; NMR analysis; SH2; crystal structures; homodimer