View source for 2jxo


==Structure of the second PDZ domain of NHERF-1==
<StructureSection load='2jxo' size='340' side='right'caption='[[2jxo]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jxo]] 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=2JXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JXO 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=2jxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jxo OCA], [https://pdbe.org/2jxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jxo RCSB], [https://www.ebi.ac.uk/pdbsum/2jxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jxo ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NHRF1_HUMAN NHRF1_HUMAN] Defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) [MIM:[https://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> 
== Function ==
[https://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> 
== 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/jx/2jxo_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=2jxo ConSurf].
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== Publication Abstract from PubMed ==
Na(+)/H(+) exchanger regulatory factor (NHERF1) is a signaling adaptor protein comprising two PDZ domains and a C-terminal ezrin-binding (EB) motif. To understand the role of intramolecular interactions in regulating its binding properties, we characterized the complex between the second PDZ domain PDZ2 and the C-terminal 242-358 fragment of NHERF1 using NMR and fluorescence methods. NMR chemical shift and relaxation data implicate 11 C-terminal residues in binding and, together with a thermodynamic analysis of mutant proteins, indicate that the EB region becomes helical when bound to PDZ2. Both specific contacts between PDZ2 and EB as well as nonspecific interactions involving a 100-residue flexible linker contribute to stabilizing two structurally distinct closed conformations of NHERF1. The affinity of mutant proteins for an extrinsic ligand is inversely related to the helix-forming propensity of the EB motif. The findings provide a structural framework for understanding how autoinhibitory interactions modulated the binding properties of NHERF1.

Autoinhibitory interactions between the PDZ2 and C-terminal domains in the scaffolding protein NHERF1.,Cheng H, Li J, Fazlieva R, Dai Z, Bu Z, Roder H Structure. 2009 May 13;17(5):660-9. PMID:19446522<ref>PMID:19446522</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2jxo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sodium-hydrogen exchange regulatory factor 3D structures|Sodium-hydrogen exchange regulatory factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bu Z]]
[[Category: Cheng H]]
[[Category: Dai Z]]
[[Category: Li J]]
[[Category: Roder H]]