Campus Units

Biochemistry, Biophysics and Molecular Biology, Bioinformatics and Computational Biology

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

4-3-2009

Journal or Book Title

Journal of Molecular Biology

Volume

387

Issue

3

First Page

726

Last Page

743

DOI

10.1016/j.jmb.2009.02.012

Abstract

We report here the NMR-derived structure of the binary complex formed by the interleukin-2 tyrosine kinase (Itk) Src homology 3 (SH3) and Src homology 2 (SH2) domains. The interaction is independent of both a phosphotyrosine motif and a proline-rich sequence, the classical targets of the SH2 and SH3 domains, respectively. The Itk SH3/SH2 structure reveals the molecular details of this nonclassical interaction and provides a clear picture for how the previously described prolyl cis/trans isomerization present in the Itk SH2 domain mediates SH3 binding. The higher-affinity cis SH2 conformer is preorganized to form a hydrophobic interface with the SH3 domain. The structure also provides insight into how autophosphorylation in the Itk SH3 domain might increase the affinity of the intermolecular SH3/SH2 interaction. Finally, we can compare this Itk complex with other examples of SH3 and SH2 domains engaging their ligands in a nonclassical manner. These small binding domains exhibit a surprising level of diversity in their binding repertoires.

Comments

This article is from Journal of Molecular Biology 387 (2009): 726–743, doi:10.1016/j.jmb.2009.02.012. Posted with permission.

Copyright Owner

Elsevier Ltd.

Language

en

File Format

application/pdf

Published Version

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