View source for 4wrn


==Crystal structure of the polymerization region of human uromodulin/Tamm-Horsfall protein==
<StructureSection load='4wrn' size='340' side='right'caption='[[4wrn]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wrn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WRN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WRN 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4wrn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wrn OCA], [https://pdbe.org/4wrn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wrn RCSB], [https://www.ebi.ac.uk/pdbsum/4wrn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wrn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/UROM_HUMAN UROM_HUMAN] UMOD-related autosomal dominant tubulointerstitial kidney disease. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/UROM_HUMAN UROM_HUMAN] Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water barrier permeability (Probable). May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF (PubMed:3498215). Facilitates neutrophil migration across renal epithelia (PubMed:20798515).<ref>PMID:20798515</ref> <ref>PMID:3498215</ref>   In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals.[UniProtKB:Q91X17][https://www.uniprot.org/uniprot/MALE_ECO57 MALE_ECO57] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite zona pellucida module (ZP-N/ZP-C), UMOD forms extracellular filaments that regulate kidney electrolyte balance and innate immunity, as well as protect against renal stones. Moreover, salt-dependent aggregation of UMOD filaments in the urine generates a soluble molecular net that captures uropathogenic bacteria and facilitates their clearance. Despite the functional importance of its homopolymers, no structural information is available on UMOD and how it self-assembles into filaments. Here, we report the crystal structures of polymerization regions of human UMOD and mouse ZP2, an essential sperm receptor protein that is structurally related to UMOD but forms heteropolymers. The structure of UMOD reveals that an extensive hydrophobic interface mediates ZP-N domain homodimerization. This arrangement is required for filament formation and is directed by an ordered ZP-N/ZP-C linker that is not observed in ZP2 but is conserved in the sequence of deafness/Crohn's disease-associated homopolymeric glycoproteins alpha-tectorin (TECTA) and glycoprotein 2 (GP2). Our data provide an example of how interdomain linker plasticity can modulate the function of structurally similar multidomain proteins. Moreover, the architecture of UMOD rationalizes numerous pathogenic mutations in both UMOD and TECTA genes.

A structured interdomain linker directs self-polymerization of human uromodulin.,Bokhove M, Nishimura K, Brunati M, Han L, de Sanctis D, Rampoldi L, Jovine L Proc Natl Acad Sci U S A. 2016 Jan 25. pii: 201519803. PMID:26811476<ref>PMID:26811476</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wrn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli O157:H7]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bokhove M]]
[[Category: De Sanctis D]]
[[Category: Jovine L]]