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PMID: 7687536 Published · ppublish English Journal Article

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

The EMBO journal ·Vol. 12 ·No. 7 ·1993-07-00 ·Pages 2617-24

Noble ME, Musacchio A, Saraste M, Courtneidge SA, Wierenga RK

Abstract

The Src-homology 3 (SH3) region is a protein domain consisting of approximately 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 A 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.

MeSH Terms
Bacterial Proteins/chemistry Base Sequence Binding Sites Carbon-Nitrogen Ligases Escherichia coli Proteins Humans Ligands Models, Molecular Molecular Sequence Data Oligodeoxyribonucleotides Protein Conformation Protein-Tyrosine Kinases/chemistry Proto-Oncogene Proteins/chemistry Proto-Oncogene Proteins c-fyn Proto-Oncogene Proteins pp60(c-src)/chemistry Repressor Proteins/chemistry Spectrin/chemistry Transcription Factors X-Ray Diffraction
Chemicals
Bacterial Proteins Escherichia coli Proteins Ligands Oligodeoxyribonucleotides Proto-Oncogene Proteins Repressor Proteins Transcription Factors Spectrin Protein-Tyrosine Kinases FYN protein, human Proto-Oncogene Proteins c-fyn Proto-Oncogene Proteins pp60(c-src) Carbon-Nitrogen Ligases birA protein, E coli
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Noble M E
EMBL, Heidelberg, Germany.
Musacchio A
Saraste M
Courtneidge S A
Wierenga R K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.2210/pdb1shf/pdb
Published
1993-07-00
Pages
2617-24
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413508
Subset
IM
External Links
PubMed source DOI: 10.2210/pdb1shf/pdb PMC Full Text View journal details
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