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9rxt
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the PDZ1 domain from human NHERF1 with the C-terminal residues (NATRL) of the human sodium-dependent phosphate transporter 2A (NaPi-IIa, SLC34A1)== | |
| + | <StructureSection load='9rxt' size='340' side='right'caption='[[9rxt]], [[Resolution|resolution]] 1.36Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9rxt]] 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=9RXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RXT FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene></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=9rxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rxt OCA], [https://pdbe.org/9rxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rxt RCSB], [https://www.ebi.ac.uk/pdbsum/9rxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rxt 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The renal solute carrier URAT1 (SLC22A12) is essential for urate homeostasis, with loss-of-function linked to renal hypouricemia, nephrolithiasis and lower gout risk. URAT1 function depends on binding the multi-PDZ domain scaffold protein PDZK1 (NHERF3), with a similar role suggested for the related NHERF1. The molecular basis of these interactions remains poorly understood. Using fluorescence anisotropy, we show that full-length human PDZK1 binds the C-terminal peptide of URAT1 with high affinity (K(D) 170 nM), unlike NHERF1 (K(D) >70 microM). The PDZ1 domain of PDZK1 alone is sufficient for high-affinity binding (K(D) 160 nM), while PDZ4 provides a secondary site (K(D) 1.35 microM), with both interactions characterized by rapid kinetics. Gel filtration shows that PDZK1 can bind two URAT1 peptides. X-ray structures of individual PDZ domains from PDZK1 and NHERF1 complexed with the URAT1 peptide reveal the underlying molecular basis for selectivity and broad affinity range. Murine Pdzk1 and Nherf1 bind Urat1 with high affinity indicating species-specific interactions. These data provide insights into URAT1 regulation by PDZ scaffold proteins with relevance for understanding urate homeostasis regulation and related disorders. | ||
| - | + | Molecular determinants of selective and high-affinity binding of the scaffold protein PDZK1 to the urate transporter URAT1.,Mymrikov EV, Wirth C, Heinicke JI, Goll J, Kern BA, Steck C, Iaroslavtceva AK, Muhlethaler T, Kottgen A, Hunte C J Mol Biol. 2025 Dec 24:169615. doi: 10.1016/j.jmb.2025.169615. PMID:41453723<ref>PMID:41453723</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9rxt" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hunte C]] | ||
| + | [[Category: Kern BA]] | ||
| + | [[Category: Mymrikov EV]] | ||
| + | [[Category: Wirth C]] | ||
Current revision
Structure of the PDZ1 domain from human NHERF1 with the C-terminal residues (NATRL) of the human sodium-dependent phosphate transporter 2A (NaPi-IIa, SLC34A1)
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