Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin

M. E.M. Noble, A. Musacchio, M. Sarasate, S. A. Courtneidge, R. K. Wierenga

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

The Src-homology 3 (SH3) region is a protein domain consisting of ~ 60 residues. It occurs in a large number of eukaryotic proteins involved in signal transduction, cell polarization and membrane-cytoskeleton interactions. The function is unknown, but it is probably involved in specific protein-protein interactions. Here we report the crystal structure of the SH3 domain of Fyn (a Src family tyrosine kinase) at 1.9 Å resolution. The crystals have two SH3 molecules per asymmetric unit. These two Fyn SH3 domains are not related by a local twofold axis. The crystal structures of spectrin and Fyn SH3 domains as well as the solution structure of the Src SH3 domain show that these all have the same basic fold. A protein domain which has the same topology as SH3 is present in the prokaryotic regulatory enzyme BirA. The comparison between the crystal structures of Fyn and spectrin SH3 domains shows that a conserved surface patch, consisting mainly of aromatic residues, is flanked by two hairpin-like loops (residues 94-104 and 114-118 in Fyn). These loops are different in tyrosine kinase and spectrin SH3 domains. They could modulate the binding properties of the aromatic surface.

Original languageEnglish (US)
Pages (from-to)2617-2624
Number of pages8
JournalEMBO Journal
Volume12
Issue number7
StatePublished - Jan 1 1993

Keywords

  • Crystal structure
  • Fyn
  • Protein - protein interactions
  • Spectrin
  • Src

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin'. Together they form a unique fingerprint.

  • Cite this