1h92: Difference between revisions

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-[[Image:1h92.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1h92", creates the "Structure Box" on the page.
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-{{STRUCTURE_1h92|  PDB=1h92  |  SCENE=  }}
-'''SH3 DOMAIN OF HUMAN LCK TYROSINE KINASE'''
+==SH3 domain of human Lck tyrosine kinase==
+<StructureSection load='1h92' size='340' side='right'caption='[[1h92]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1h92]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H92 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1h92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h92 OCA], [https://pdbe.org/1h92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h92 RCSB], [https://www.ebi.ac.uk/pdbsum/1h92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h92 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
+== Function ==
+[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h9/1h92_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1h92 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that interacts with both the SH3 domain and the kinase domain of the T-cell-specific tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is considered as a key event in the transformation of human T-lymphocytes during herpesviral infection. We investigated the interaction of proline-rich Tip peptides with the LckSH3 domain starting with the structural characterization of the unbound interaction partners. The solution structure of the LckSH3 was determined by heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopy using 44 residual dipolar couplings in addition to the conventional experimental restraints. Circular dichroism spectroscopy proved that the polyproline helix of Tip is already formed prior to SH3 binding and is conformationally stable. NMR titration experiments point out three major regions of the Tip-Lck interaction comprising the RT loop, the n-src loop, and a helical turn preceding the last strand of the beta-sheet. Further changes of the chemical shifts were observed for the N- and C-terminal beta-strands of the SH3 domain, indicating additional contacts outside the proline-rich segment or subtle structural rearrangements transmitted from the binding site of the proline helix. Fluorescence spectroscopy shows that Tip binds to the SH3 domains of several Src kinases (Lck, Hck, Lyn, Src, Fyn, Yes), exhibiting the highest affinities for Lyn, Hck, and Lck.
-==Overview==
+Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck.,Schweimer K, Hoffmann S, Bauer F, Friedrich U, Kardinal C, Feller SM, Biesinger B, Sticht H Biochemistry. 2002 Apr 23;41(16):5120-30. PMID:11955060<ref>PMID:11955060</ref>
-Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that interacts with both the SH3 domain and the kinase domain of the T-cell-specific tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is considered as a key event in the transformation of human T-lymphocytes during herpesviral infection. We investigated the interaction of proline-rich Tip peptides with the LckSH3 domain starting with the structural characterization of the unbound interaction partners. The solution structure of the LckSH3 was determined by heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopy using 44 residual dipolar couplings in addition to the conventional experimental restraints. Circular dichroism spectroscopy proved that the polyproline helix of Tip is already formed prior to SH3 binding and is conformationally stable. NMR titration experiments point out three major regions of the Tip-Lck interaction comprising the RT loop, the n-src loop, and a helical turn preceding the last strand of the beta-sheet. Further changes of the chemical shifts were observed for the N- and C-terminal beta-strands of the SH3 domain, indicating additional contacts outside the proline-rich segment or subtle structural rearrangements transmitted from the binding site of the proline helix. Fluorescence spectroscopy shows that Tip binds to the SH3 domains of several Src kinases (Lck, Hck, Lyn, Src, Fyn, Yes), exhibiting the highest affinities for Lyn, Hck, and Lck.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-H92 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H92 OCA].
+</div>
+<div class="pdbe-citations 1h92" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck., Schweimer K, Hoffmann S, Bauer F, Friedrich U, Kardinal C, Feller SM, Biesinger B, Sticht H, Biochemistry. 2002 Apr 23;41(16):5120-30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11955060 11955060]
+*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Biesinger, B.]]
+[[Category: Biesinger B]]
-[[Category: Friedrich, U.]]
+[[Category: Friedrich U]]
-[[Category: Hoffmann, S.]]
+[[Category: Hoffmann S]]
-[[Category: Roesch, P.]]
+[[Category: Roesch P]]
-[[Category: Schweimer, K.]]
+[[Category: Schweimer K]]
-[[Category: Sticht, H.]]
+[[Category: Sticht H]]
-[[Category: Lck]]
-[[Category: Sh3 domain]]
-[[Category: Signal transduction]]
-[[Category: Tyrosine kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:35:12 2008''