1G83

CRYSTAL STRUCTURE OF FYN SH3-SH2

Summary for 1G83

• Entry DOI: 10.2210/pdb1g83/pdb
• Descriptor: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE FYN (2 entities in total)
• Functional Keywords: beta barrel, antiparallel beta sheet, alpha helix, 3-10 helix, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane: P06241
• Total number of polymer chains: 2
• Total formula weight: 37821.86

Authors

Arold, S.T.,Ulmer, T.S.,Mulhern, T.D.,Werner, J.M.,Ladbury, J.E.,Campbell, I.D.,Noble, M.E.M. (deposition date: 2000-11-16, release date: 2001-05-30, Last modification date: 2024-02-07)

Primary citation

Arold, S.T.,Ulmer, T.S.,Mulhern, T.D.,Werner, J.M.,Ladbury, J.E.,Campbell, I.D.,Noble, M.E.
The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases.
J.Biol.Chem., 276:17199-17205, 2001

PubMed Abstract: The regulatory fragment of Src kinases, comprising Src homology (SH) 3 and SH2 domains, is responsible for controlled repression of kinase activity. We have used a multidisciplinary approach involving crystallography, NMR, and isothermal titration calorimetry to study the regulatory fragment of Fyn (FynSH32) and its interaction with a physiological activator: a fragment of focal adhesion kinase that contains both phosphotyrosine and polyproline motifs. Although flexible, the preferred disposition of SH3 and SH2 domains in FynSH32 resembles the inactive forms of Hck and Src, differing significantly from LckSH32. This difference, which results from variation in the SH3-SH2 linker sequences, will affect the potential of the regulatory fragments to repress kinase activity. This surprising result implies that the mechanism of repression of Src family members may vary, explaining functional distinctions between Fyn and Lck. The interaction between FynSH32 and focal adhesion kinase is restricted to the canonical SH3 and SH2 binding sites and does not affect the dynamic independence of the two domains. Consequently, the interaction shows no enhancement by an avidity effect. Such an interaction may have evolved to gain specificity through an extended recognition site while maintaining rapid dissociation after signaling.

PubMed: 11278857
DOI: 10.1074/jbc.M011185200

Experimental method

X-RAY DIFFRACTION (2.6 Å)