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4p0c

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==Crystal Structure of NHERF2 PDZ1 Domain in Complex with LPA2==
==Crystal Structure of NHERF2 PDZ1 Domain in Complex with LPA2==
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<StructureSection load='4p0c' size='340' side='right' caption='[[4p0c]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
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<StructureSection load='4p0c' size='340' side='right'caption='[[4p0c]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4p0c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P0C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P0C FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4p0c]] is a 1 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=4P0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P0C FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.339&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p0c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p0c RCSB], [http://www.ebi.ac.uk/pdbsum/4p0c PDBsum]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
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<table>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4p0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p0c OCA], [https://pdbe.org/4p0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p0c RCSB], [https://www.ebi.ac.uk/pdbsum/4p0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p0c ProSAT]</span></td></tr>
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<div style="background-color:#fffaf0;">
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</table>
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== Publication Abstract from PubMed ==
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== Function ==
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The formation of CFTR-NHERF2-LPA2 macromolecular complex in airway epithelia regulates CFTR channel function and plays an important role in compartmentalized cAMP signaling. We previously have shown that disruption of the PDZ-mediated NHERF2-LPA2 interaction abolishes the LPA inhibitory effect and augments CFTR Cl(-) channel activity in vitro and in vivo. Here we report the first crystal structure of the NHERF2 PDZ1 domain in complex with the C-terminal LPA2 sequence. The structure reveals that the PDZ1-LPA2 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four LPA2 residues contributing to specific interactions. Comparison of the PDZ1-LPA2 structure to the structure of PDZ1 in complex with a different peptide provides insights into the diverse nature of PDZ1 substrate recognition and suggests that the conformational flexibility in the ligand binding pocket is involved in determining the broad substrate specificity of PDZ1. In addition, the structure reveals a small surface pocket adjacent to the ligand-binding site, which may have therapeutic implications. This study provides an understanding of the structural basis for the PDZ-mediated NHERF2-LPA2 interaction that could prove valuable in selective drug design against CFTR-related human diseases.
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[https://www.uniprot.org/uniprot/NHRF2_HUMAN NHRF2_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 cAMP-mediated phosphorylation and inhibition of SLC9A3. May also act as scaffold protein in the nucleus.<ref>PMID:9096337</ref> <ref>PMID:10455146</ref>
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Structural insights into PDZ-mediated interaction of NHERF2 and LPA(2), a cellular event implicated in CFTR channel regulation.,Holcomb J, Jiang Y, Lu G, Trescott L, Brunzelle J, Sirinupong N, Li C, Naren AP, Yang Z Biochem Biophys Res Commun. 2014 Mar 28;446(1):399-403. doi:, 10.1016/j.bbrc.2014.02.128. Epub 2014 Mar 12. PMID:24613836<ref>PMID:24613836</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Lysophosphatidic acid receptor|Lysophosphatidic acid receptor]]
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*[[Sandbox Reserved 1789|Sandbox Reserved 1789]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Brunzelle, J.]]
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[[Category: Homo sapiens]]
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[[Category: Holcomb, J.]]
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[[Category: Large Structures]]
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[[Category: Jiang, Y.]]
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[[Category: Brunzelle J]]
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[[Category: Li, C.]]
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[[Category: Holcomb J]]
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[[Category: Lu, G.]]
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[[Category: Jiang Y]]
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[[Category: Naren, A.]]
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[[Category: Li C]]
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[[Category: Sirinupong, N.]]
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[[Category: Lu G]]
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[[Category: Trescott, L.]]
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[[Category: Naren A]]
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[[Category: Yang, Z.]]
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[[Category: Sirinupong N]]
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[[Category: Pdz]]
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[[Category: Trescott L]]
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[[Category: Protein binding]]
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[[Category: Yang Z]]
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[[Category: Protein-protein interaction]]
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Current revision

Crystal Structure of NHERF2 PDZ1 Domain in Complex with LPA2

PDB ID 4p0c

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