4jl7

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{{STRUCTURE_4jl7| PDB=4jl7 | SCENE= }}
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==Crystal Structure of the Chemokine Receptor CXCR2 in Complex with the First PDZ Domain of NHERF1==
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===Crystal Structure of the Chemokine Receptor CXCR2 in Complex with the First PDZ Domain of NHERF1===
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<StructureSection load='4jl7' size='340' side='right' caption='[[4jl7]], [[Resolution|resolution]] 1.16&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24098448}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4jl7]] is a 1 chain structure with 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=4JL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JL7 FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NHERF, NHERF1, SLC9A3R1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=4jl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jl7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jl7 RCSB], [http://www.ebi.ac.uk/pdbsum/4jl7 PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/NHRF1_HUMAN NHRF1_HUMAN]] Defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) [MIM:[http://omim.org/entry/612287 612287]]. Hypophosphatemia results from idiopathic renal phosphate loss. It contributes to the pathogenesis of hypophosphatemic urolithiasis (formation of urinary calculi) as well to that of hypophosphatemic osteoporosis (bone demineralization).<ref>PMID:18784102</ref> <ref>PMID:22506049</ref>
[[http://www.uniprot.org/uniprot/NHRF1_HUMAN NHRF1_HUMAN]] Defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) [MIM:[http://omim.org/entry/612287 612287]]. Hypophosphatemia results from idiopathic renal phosphate loss. It contributes to the pathogenesis of hypophosphatemic urolithiasis (formation of urinary calculi) as well to that of hypophosphatemic osteoporosis (bone demineralization).<ref>PMID:18784102</ref> <ref>PMID:22506049</ref>
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== Function ==
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==Function==
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[[http://www.uniprot.org/uniprot/NHRF1_HUMAN NHRF1_HUMAN]] Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules.<ref>PMID:9430655</ref> <ref>PMID:9096337</ref> <ref>PMID:10499588</ref> <ref>PMID:18784102</ref>
[[http://www.uniprot.org/uniprot/NHRF1_HUMAN NHRF1_HUMAN]] Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules.<ref>PMID:9430655</ref> <ref>PMID:9096337</ref> <ref>PMID:10499588</ref> <ref>PMID:18784102</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Neutrophil plays an essential role in host defense against infection, but uncontrolled neutrophilic infiltration can cause inflammation and severe epithelial damage. We recently showed that CXCR2 formed a signaling complex with NHERF1 and PLC-2, and that the formation of this complex was required for intracellular calcium mobilization and neutrophilic transepithelial migration. To uncover the structural basis of the complex formation, we report here the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal sequence of CXCR2 at 1.16 A resolution. The structure reveals that the CXCR2 peptide binds to PDZ1 in an extended conformation with the last four residues making specific side chain interactions. Remarkably, comparison of the structure to previously studied PDZ1 domains has allowed the identification of PDZ1 ligand-specific interactions and the mechanisms that govern PDZ1 target selection diversities. In addition, we show that CXCR2 can bind both NHERF1 PDZ1 and PDZ2 in pulldown experiments, consistent with the observation that the peptide binding pockets of these two PDZ domains are highly structurally conserved. The results of this study therefore provide structural basis for the CXCR2-mediated neutrophilic migration and could have important clinical applications in the prevention and treatment of numerous neutrophil-dependent inflammatory disorders.
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==About this Structure==
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Structural Insights into Neutrophilic Migration Revealed by the Crystal Structure of the Chemokine Receptor CXCR2 in Complex with the First PDZ Domain of NHERF1.,Lu G, Wu Y, Jiang Y, Wang S, Hou Y, Guan X, Brunzelle J, Sirinupong N, Sheng S, Li C, Yang Z PLoS One. 2013 Oct 2;8(10):e76219. doi: 10.1371/journal.pone.0076219. PMID:24098448<ref>PMID:24098448</ref>
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[[4jl7]] is a 1 chain structure with 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=4JL7 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024098448</ref><references group="xtra"/><references/>
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</div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Brunzelle, J.]]
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[[Category: Brunzelle, J]]
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[[Category: Jiang, Y.]]
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[[Category: Jiang, Y]]
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[[Category: Li, C.]]
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[[Category: Li, C]]
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[[Category: Lu, G.]]
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[[Category: Lu, G]]
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[[Category: Sirinupong, N.]]
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[[Category: Sirinupong, N]]
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[[Category: Wu, Y.]]
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[[Category: Wu, Y]]
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[[Category: Yang, Z.]]
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[[Category: Yang, Z]]
[[Category: Cxcr2]]
[[Category: Cxcr2]]
[[Category: Inflammatory disease]]
[[Category: Inflammatory disease]]

Revision as of 15:03, 21 December 2014

Crystal Structure of the Chemokine Receptor CXCR2 in Complex with the First PDZ Domain of NHERF1

4jl7, resolution 1.16Å

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