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2m0u

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Current revision

Complex structure of C-terminal CFTR peptide and extended PDZ1 domain from NHERF1

Structural highlights

2m0u is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NHRF1_HUMAN Defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) [MIM: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).^[1] ^[2]

Function

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.^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

The multi-domain scaffolding protein NHERF1 modulates the assembly and intracellular trafficking of various transmembrane receptors and ion-transport proteins. The two PDZ (postsynaptic density 95/disk large/zonula occluden 1) domains of NHERF1 possess very different ligand-binding capabilities: PDZ1 recognizes a variety of membrane proteins with high affinity, while PDZ2 only binds limited number of target proteins. Here using NMR, we have determined the structural and dynamic mechanisms that differentiate the binding affinities of the two PDZ domains, for the type 1 PDZ-binding motif (QDTRL) in the carboxyl terminus of cystic fibrosis transmembrane regulator. Similar to PDZ2, we have identified a helix-turn-helix subdomain coupled to the canonical PDZ1 domain. The extended PDZ1 domain is highly flexible with correlated backbone motions on fast and slow timescales, while the extended PDZ2 domain is relatively rigid. The malleability of the extended PDZ1 structure facilitates the transmission of conformational changes at the ligand-binding site to the remote helix-turn-helix extension. By contrast, ligand binding has only modest effects on the conformation and dynamics of the extended PDZ2 domain. The study shows that ligand-induced structural and dynamic changes coupled with sequence variation at the putative PDZ binding site dictate ligand selectivity and binding affinity of the two PDZ domains of NHERF1.

Ligand-Induced Dynamic Changes in Extended PDZ Domains from NHERF1.,Bhattacharya S, Ju JH, Orlova N, Khajeh JA, Cowburn D, Bu Z J Mol Biol. 2013 Apr 10. pii: S0022-2836(13)00209-X. doi:, 10.1016/j.jmb.2013.04.001. PMID:23583913^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. PMID:18784102 doi:359/11/1128
↑ Courbebaisse M, Leroy C, Bakouh N, Salaun C, Beck L, Grandchamp B, Planelles G, Hall RA, Friedlander G, Prie D. A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism. PLoS One. 2012;7(4):e34764. doi: 10.1371/journal.pone.0034764. Epub 2012 Apr 10. PMID:22506049 doi:10.1371/journal.pone.0034764
↑ Murthy A, Gonzalez-Agosti C, Cordero E, Pinney D, Candia C, Solomon F, Gusella J, Ramesh V. NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J Biol Chem. 1998 Jan 16;273(3):1273-6. PMID:9430655
↑ Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M. cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3010-5. PMID:9096337
↑ Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. PMID:10499588 doi:10.1038/45816
↑ Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. PMID:18784102 doi:359/11/1128
↑ Bhattacharya S, Ju JH, Orlova N, Khajeh JA, Cowburn D, Bu Z. Ligand-Induced Dynamic Changes in Extended PDZ Domains from NHERF1. J Mol Biol. 2013 Apr 10. pii: S0022-2836(13)00209-X. doi:, 10.1016/j.jmb.2013.04.001. PMID:23583913 doi:10.1016/j.jmb.2013.04.001

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m0u"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2m0u]] is a 2 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=2M0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M0U FirstGlance]. <br>
-</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=2m0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0u OCA], [https://pdbe.org/2m0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0u RCSB], [https://www.ebi.ac.uk/pdbsum/2m0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0u ProSAT]</span></td></tr>
+</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=2m0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0u OCA], [https://pdbe.org/2m0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0u RCSB], [https://www.ebi.ac.uk/pdbsum/2m0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0u ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 ==See Also==
-*[[Sodium-hydrogen exchange regulatory factor|Sodium-hydrogen exchange regulatory factor]]
+*[[Sodium-hydrogen exchange regulatory factor 3D structures|Sodium-hydrogen exchange regulatory factor 3D structures]]
 == References ==
 <references/>

2m0u

From Proteopedia

Current revision

Complex structure of C-terminal CFTR peptide and extended PDZ1 domain from NHERF1

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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