1AWJ

INTRAMOLECULAR ITK-PROLINE COMPLEX, NMR, MINIMIZED AVERAGE STRUCTURE

Summary for 1AWJ

• Entry DOI: 10.2210/pdb1awj/pdb
• Descriptor: ITK (1 entity in total)
• Functional Keywords: transferase, regulatory intramolecular complex, kinase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell membrane: Q03526
• Total number of polymer chains: 1
• Total formula weight: 9139.96

Authors

Andreotti, A.H.,Bunnell, S.C.,Feng, S.,Berg, L.J.,Schreiber, S.L. (deposition date: 1997-10-02, release date: 1998-01-14, Last modification date: 2024-05-22)

Primary citation

Andreotti, A.H.,Bunnell, S.C.,Feng, S.,Berg, L.J.,Schreiber, S.L.
Regulatory intramolecular association in a tyrosine kinase of the Tec family.
Nature, 385:93-97, 1997

PubMed Abstract: The T-cell-specific tyrosine kinase Itk is a member of the Tec family of non-receptor tyrosine kinases, and is required for signalling through the T-cell antigen receptor (TCR). The role of Itk in TCR signalling and the manner in which Itk activity is regulated are not well understood. Substrate binding and enzymatic activity of the structurally related Src kinases are regulated by an intramolecular interaction between the Src-homology-2 (SH2) domain and a phosphotyrosine. Although Itk also contains SH3, SH2 and tyrosine kinase domains, it lacks the corresponding regulatory phosphorylation site, and therefore must be regulated by an alternative mechanism. The proline-rich sequence adjacent to the SH3 domain of Tec family kinases contains an SH3 ligand, potentially allowing a different intramolecular interaction. By using multidimensional nuclear magnetic resonance we have determined the structure of a fragment of Itk, confirming that these domains interact intramolecularly. Formation of this intramolecular SH3-ligand complex prevents the Itk SH3 domain and proline-rich region from interacting with their respective protein ligands, Sam68 and Grb-2. We believe that this structure represents the first example of an intramolecular interaction between an SH3 domain and a proline-rich ligand, and has implications for the regulation of Tec family kinases.

PubMed: 8985255
DOI: 10.1038/385093a0

Experimental method

SOLUTION NMR