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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology

2009

Series

Itk

Articles 1 - 2 of 2

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Proline Isomerization Preorganizes The Itk Sh2 Domain For Binding The Itk Sh3 Domain, Andrew J. Severin, Raji E. Joseph, Scott E. Boyken, D. Bruce Fulton, Amy H. Andreotti Apr 2009

Proline Isomerization Preorganizes The Itk Sh2 Domain For Binding The Itk Sh3 Domain, Andrew J. Severin, Raji E. Joseph, Scott E. Boyken, D. Bruce Fulton, Amy H. Andreotti

Biochemistry, Biophysics and Molecular Biology Publications

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 ...


Conformational Snapshots Of Tec Kinases During Signaling, Raji E. Joseph, Amy H. Andreotti Mar 2009

Conformational Snapshots Of Tec Kinases During Signaling, Raji E. Joseph, Amy H. Andreotti

Biochemistry, Biophysics and Molecular Biology Publications

The control of cellular signaling cascades is of utmost importance in regulating the immune response. Exquisitely precise protein-protein interactions and chemical modification of substrates by enzymatic catalysis are the fundamental components of the signals that alert immune cells to the presence of a foreign antigen. In particular, the phosphorylation events induced by protein kinase activity must be spatially and temporally regulated by specific interactions to maintain a normal and effective immune response. High resolution structures of many protein kinases along with supporting biochemical data are providing significant insight into the intricate regulatory mechanisms responsible for controlling cellular signaling. The Tec ...