1GL5: NMR structure of the SH3 domain from the Tec protein tyrosine kinase

Tec is the prototypic member of a family of intracellular tyrosine kinases that includes Txk, Bmx, Itk, and Btk. Tec family kinases share similarities in domain structure with Src family kinases, but one of the features that differentiates them is a proline-rich region (PRR) preceding their Src homology (SH) 3 domain. Evidence that the PRR of Itk can bind in an intramolecular fashion to its SH3 domain and the lack of a regulatory tyrosine in the C terminus indicates that Tec kinases must be regulated by a different set of intramolecular interactions to the Src kinases. We have determined the solution structure of the Tec SH3 domain and have investigated interactions with its PRR, which contains two SH3-binding sites. We demonstrate that in vitro, the Tec PRR can bind in an intramolecular fashion to the SH3. However, the affinity is lower than that for dimerization via reciprocal PRR-SH3 association. Using site-directed mutagenesis we show that both sites can bind the Tec SH3 domain; site 1 (155KTLPPAP161) binds intramolecularly, while site 2 (165KRRPPPPIPP174) cannot and binds in an intermolecular fashion. These distinct roles for the SH3 binding sites in Tec family kinases could be important for protein targeting and enzyme activation.
PDB ID: 1GL5Download
MMDB ID: 18004
PDB Deposition Date: 2001/8/28
Updated in MMDB: 2001/12
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 1GL5: monomeric; determined by author
Molecular Components in 1GL5
Label Count Molecule
Protein (1 molecule)
Tyrosine-protein Kinase TEC(Gene symbol: Tec)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB