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

Martin E M Noble, Andrea Musacchio, Matti Saraste, Sara Courtneidge, Rik K. Wierenga

Research output: Contribution to journalArticle

187 Citations (Scopus)

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 - 1993
Externally publishedYes

Fingerprint

Spectrin
src Homology Domains
Protein-Tyrosine Kinases
Crystal structure
Proteins
Signal transduction
src-Family Kinases
Surface Properties
Cytoskeleton
Topology
Signal Transduction
Polarization
Membranes
Crystals
Cell Membrane
Molecules
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin. / Noble, Martin E M; Musacchio, Andrea; Saraste, Matti; Courtneidge, Sara; Wierenga, Rik K.

In: EMBO Journal, Vol. 12, No. 7, 1993, p. 2617-2624.

Research output: Contribution to journalArticle

Noble, Martin E M ; Musacchio, Andrea ; Saraste, Matti ; Courtneidge, Sara ; Wierenga, Rik K. / Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin. In: EMBO Journal. 1993 ; Vol. 12, No. 7. pp. 2617-2624.
@article{09b7e748979842ec82bf5d9872304220,
title = "Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin",
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 {\AA} 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.",
keywords = "Crystal structure, Fyn, Protein - Protein interactions, Spectrin, Src",
author = "Noble, {Martin E M} and Andrea Musacchio and Matti Saraste and Sara Courtneidge and Wierenga, {Rik K.}",
year = "1993",
language = "English (US)",
volume = "12",
pages = "2617--2624",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Crystal structure of the SH3 domain in human Fyn; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and spectrin

AU - Noble, Martin E M

AU - Musacchio, Andrea

AU - Saraste, Matti

AU - Courtneidge, Sara

AU - Wierenga, Rik K.

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

KW - Crystal structure

KW - Fyn

KW - Protein - Protein interactions

KW - Spectrin

KW - Src

UR - http://www.scopus.com/inward/record.url?scp=0027245080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027245080&partnerID=8YFLogxK

M3 - Article

VL - 12

SP - 2617

EP - 2624

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 7

ER -