1gl5
From Proteopedia
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NMR STRUCTURE OF THE SH3 DOMAIN FROM THE TEC PROTEIN TYROSINE KINASE
Overview
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.
About this Structure
1GL5 is a Single protein structure of sequence from Mus musculus. Active as Transferase, with EC number 2.7.1.112. Full crystallographic information is available from OCA.
Reference
The solution structure and intramolecular associations of the Tec kinase SRC homology 3 domain., Pursglove SE, Mulhern TD, Mackay JP, Hinds MG, Booker GW, J Biol Chem. 2002 Jan 4;277(1):755-62. Epub 2001 Oct 29. PMID:11684687
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