کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2186662 | 1096070 | 2009 | 18 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Proline Isomerization Preorganizes the Itk SH2 Domain for Binding to the Itk SH3 Domain Proline Isomerization Preorganizes the Itk SH2 Domain for Binding to the Itk SH3 Domain](/preview/png/2186662.png)
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.
Journal: Journal of Molecular Biology - Volume 387, Issue 3, 3 April 2009, Pages 726–743