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2eu0

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Revision as of 05:19, 11 September 2015

The NMR ensemble structure of the Itk SH2 domain bound to a phosphopeptide

Structural highlights

2eu0 is a 2 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	, ,
Related:	1lui, 1luk, 1lum, 1lun, 2etz
Gene:	Itk, Emt, Tlk, Tsk (LK3 transgenic mice)
Activity:	Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[ITK_MOUSE] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.^[1] [LCP2_MOUSE] Involved in T-cell antigen receptor mediated signaling.^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Src homology 2 (SH2) domain of interleukin-2 tyrosine kinase (Itk) is a critical component of the regulatory apparatus controlling the activity of this immunologically important enzyme. To gain insight into the structural features associated with the activated form of Itk, we have solved the NMR structure of the SH2 domain bound to a phosphotyrosine-containing peptide (pY) and analyzed changes in trans-hydrogen bond scalar couplings ((3h)J(NC')) that result from pY binding. Isomerization of a single prolyl imide bond in this domain is responsible for simultaneous existence of two distinct SH2 conformers. Prolyl isomerization directs ligand recognition: the trans conformer preferentially binds pY. The structure of the SH2/pY complex provides insight into the ligand specificity; the BG loop in the ligand-free trans SH2 conformer is pre-arranged for optimal contacts with the pY+3 residue of the ligand. Analysis of (3h)J(NC') couplings arising from hydrogen bonds has revealed propagation of structural changes from the pY binding pocket to the CD loop containing conformationally heterogeneous proline as well as to the alphaB helix, on the opposite site of the domain. These findings offer a structural framework for understanding the roles of prolyl isomerization and pY binding in Itk regulation.

Molecular details of Itk activation by prolyl isomerization and phospholigand binding: the NMR structure of the Itk SH2 domain bound to a phosphopeptide.,Pletneva EV, Sundd M, Fulton DB, Andreotti AH J Mol Biol. 2006 Mar 24;357(2):550-61. Epub 2006 Jan 18. PMID:16436281^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Qi Q, Xia M, Bai Y, Yu S, Cantorna M, August A. Interleukin-2-inducible T cell kinase (Itk) network edge dependence for the maturation of iNKT cell. J Biol Chem. 2011 Jan 7;286(1):138-46. doi: 10.1074/jbc.M110.148205. Epub 2010, Oct 29. PMID:21036902 doi:http://dx.doi.org/10.1074/jbc.M110.148205
↑ Schneider H, Guerette B, Guntermann C, Rudd CE. Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells. J Biol Chem. 2000 Feb 11;275(6):3835-40. PMID:10660534
↑ Pletneva EV, Sundd M, Fulton DB, Andreotti AH. Molecular details of Itk activation by prolyl isomerization and phospholigand binding: the NMR structure of the Itk SH2 domain bound to a phosphopeptide. J Mol Biol. 2006 Mar 24;357(2):550-61. Epub 2006 Jan 18. PMID:16436281 doi:http://dx.doi.org/10.1016/j.jmb.2005.12.073

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2eu0"

@@ Line 2: / Line 2: @@
 <StructureSection load='2eu0' size='340' side='right' caption='[[2eu0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2eu0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2EU0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2eu0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2EU0 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lui|1lui]], [[1luk|1luk]], [[1lum|1lum]], [[1lun|1lun]], [[2etz|2etz]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Itk, Emt, Tlk, Tsk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Itk, Emt, Tlk, Tsk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2eu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eu0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2eu0 RCSB], [http://www.ebi.ac.uk/pdbsum/2eu0 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2eu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eu0 OCA], [http://pdbe.org/2eu0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2eu0 RCSB], [http://www.ebi.ac.uk/pdbsum/2eu0 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2eu0" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Transferase]]
 [[Category: Andreotti, A H]]

2eu0

From Proteopedia

Revision as of 05:19, 11 September 2015

The NMR ensemble structure of the Itk SH2 domain bound to a phosphopeptide

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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