2oq1: Difference between revisions

<StructureSection load='2oq1' size='340' side='right'caption='[[2oq1]], [[Resolution|resolution]] 1.90&Aring;' scene=''>

== Structural highlights ==

<table><tr><td colspan='2'>[[2oq1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OQ1 FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2oq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oq1 OCA], [https://pdbe.org/2oq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oq1 RCSB], [https://www.ebi.ac.uk/pdbsum/2oq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oq1 ProSAT]</span></td></tr>

== Disease ==

[https://www.uniprot.org/uniprot/ZAP70_HUMAN ZAP70_HUMAN] Defects in ZAP70 are the cause of selective T-cell defect (STCD) [MIM:[https://omim.org/entry/269840 269840]. A form of severe combined immunodeficiency characterized by a selective absence of CD8+ T cells.<ref>PMID:8124727</ref> <ref>PMID:8202713</ref> <ref>PMID:11412303</ref> <ref>PMID:11123350</ref> <ref>PMID:18509675</ref>

== Function ==

[https://www.uniprot.org/uniprot/ZAP70_HUMAN ZAP70_HUMAN] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).<ref>PMID:1423621</ref> <ref>PMID:8124727</ref> <ref>PMID:8702662</ref> <ref>PMID:9489702</ref> <ref>PMID:11353765</ref>

== Evolutionary Conservation ==

[[Image:Consurf_key_small.gif|200px|right]]

</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2oq1 ConSurf].

<div style="clear:both"></div>

<div style="background-color:#fffaf0;">

Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor.,Hatada MH, Lu X, Laird ER, Green J, Morgenstern JP, Lou M, Marr CS, Phillips TB, Ram MK, Theriault K, et al. Nature. 1995 Sep 7;377(6544):32-8. PMID:7659156<ref>PMID:7659156</ref>

==See Also==

*[[CD3 3D structures|CD3 3D structures]]

*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]

== References ==

<references/>

</StructureSection>

[[Category: Large Structures]]

[[Category: Green J]]

[[Category: Hatada MH]]

[[Category: Laird ER]]

[[Category: Morgenstern J]]

[[Category: Ram MK]]