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6h6a
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of UNC119 in complex with LCK peptide== | |
| + | <StructureSection load='6h6a' size='340' side='right'caption='[[6h6a]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6h6a]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H6A FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=15P:POLYETHYLENE+GLYCOL+(N=34)'>15P</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UNC119, RG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6h6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h6a OCA], [http://pdbe.org/6h6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h6a RCSB], [http://www.ebi.ac.uk/pdbsum/6h6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h6a ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN]] Idiopathic CD4 lymphocytopenia;Cone rod dystrophy. Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN]] Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Binds myristoylated NPHP3; however, in contrast to UNC119B, does not seem to play a major role in ciliary membrane localization of NPHP3. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells.<ref>PMID:22085962</ref> <ref>PMID:21642972</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a "regulatory arm" by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse. | ||
| - | + | The Ciliary Machinery Is Repurposed for T Cell Immune Synapse Trafficking of LCK.,Stephen LA, ElMaghloob Y, McIlwraith MJ, Yelland T, Castro Sanchez P, Roda-Navarro P, Ismail S Dev Cell. 2018 Oct 8;47(1):122-132.e4. doi: 10.1016/j.devcel.2018.08.012. Epub, 2018 Sep 13. PMID:30220567<ref>PMID:30220567</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6h6a" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: ElMaghloob, Y]] | ||
| + | [[Category: Ismail, S]] | ||
| + | [[Category: McIlwraith, M]] | ||
| + | [[Category: Stephen, L]] | ||
| + | [[Category: Yelland, T]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Transport]] | ||
Current revision
Crystal structure of UNC119 in complex with LCK peptide
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Categories: Human | Large Structures | ElMaghloob, Y | Ismail, S | McIlwraith, M | Stephen, L | Yelland, T | Complex | Immune system | Kinase | Transport
