1g9o: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==FIRST PDZ DOMAIN OF THE HUMAN NA+/H+ EXCHANGER REGULATORY FACTOR== | |||
<StructureSection load='1g9o' size='340' side='right' caption='[[1g9o]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1g9o]] 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=1G9O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G9O FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NHERF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<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=1g9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g9o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1g9o RCSB], [http://www.ebi.ac.uk/pdbsum/1g9o PDBsum]</span></td></tr> | |||
<table> | |||
== 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> | |||
== Function == | |||
[[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> | |||
== 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/g9/1g9o_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Na(+)/H(+) exchanger regulatory factor (NHERF; also known as EBP50) contains two PDZ domains that mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. The NHERF PDZ1 domain interacts specifically with the motifs DSLL, DSFL, and DTRL present at the carboxyl termini of the beta(2) adrenergic receptor (beta(2)AR), the platelet-derived growth factor receptor (PDGFR), and the cystic fibrosis transmembrane conductance regulator (CFTR), respectively, and plays a central role in the physiological regulation of these proteins. The crystal structure of the human NHERF PDZ1 has been determined at 1.5 A resolution using multiwavelength anomalous diffraction phasing. The overall structure is similar to known PDZ structures, with notable differences in the NHERF PDZ1 carboxylate-binding loop that contains the GYGF motif, and the variable loop between the beta2 and beta3 strands. In the crystalline state, the carboxyl-terminal sequence DEQL of PDZ1 occupies the peptide-binding pocket of a neighboring PDZ1 molecule related by 2-fold crystallographic symmetry. This structure reveals the molecular mechanism of carboxyl-terminal leucine recognition by class I PDZ domains, and provides insights into the specificity of NHERF interaction with the carboxyl termini of several membrane receptors and ion channels, including the beta(2)AR, PDGFR, and CFTR. | |||
Crystal structure of the PDZ1 domain of human Na(+)/H(+) exchanger regulatory factor provides insights into the mechanism of carboxyl-terminal leucine recognition by class I PDZ domains.,Karthikeyan S, Leung T, Birrane G, Webster G, Ladias JA J Mol Biol. 2001 May 18;308(5):963-73. PMID:11352585<ref>PMID:11352585</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Birrane, G.]] | [[Category: Birrane, G.]] | ||