1gl5
From Proteopedia
(New page: 200px<br /><applet load="1gl5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gl5" /> '''NMR STRUCTURE OF THE SH3 DOMAIN FROM THE TEC...) |
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| - | [[Image:1gl5.jpg|left|200px]]<br /><applet load="1gl5" size=" | + | [[Image:1gl5.jpg|left|200px]]<br /><applet load="1gl5" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''NMR STRUCTURE OF THE SH3 DOMAIN FROM THE TEC PROTEIN TYROSINE KINASE'''<br /> | '''NMR STRUCTURE OF THE SH3 DOMAIN FROM THE TEC PROTEIN TYROSINE KINASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Tec is the prototypic member of a family of intracellular tyrosine kinases | + | 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== | ==About this Structure== | ||
| - | 1GL5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.112. 2.7.1.112.] Full crystallographic information is available from [http:// | + | 1GL5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.112. 2.7.1.112.] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GL5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Booker, G | + | [[Category: Booker, G W.]] |
| - | [[Category: Mulhern, T | + | [[Category: Mulhern, T D.]] |
| - | [[Category: Pursglove, S | + | [[Category: Pursglove, S E.]] |
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:51:19 2008'' |
Revision as of 10:51, 21 February 2008
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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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