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| ==Cryo-EM of native human uromodulin (UMOD)/Tamm-Horsfall protein (THP) filament.== | | ==Cryo-EM of native human uromodulin (UMOD)/Tamm-Horsfall protein (THP) filament== |
| <StructureSection load='6tqk' size='340' side='right'caption='[[6tqk]], [[Resolution|resolution]] 3.35Å' scene=''> | | <StructureSection load='6tqk' size='340' side='right'caption='[[6tqk]], [[Resolution|resolution]] 3.35Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6tqk]] is a 3 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=6TQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TQK FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TQK FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.35Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4wrn|4wrn]], [[3nk4|3nk4]], [[6tql|6tql]]</div></td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6tqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqk OCA], [https://pdbe.org/6tqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tqk RCSB], [https://www.ebi.ac.uk/pdbsum/6tqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqk ProSAT]</span></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=6tqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqk OCA], [https://pdbe.org/6tqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tqk RCSB], [https://www.ebi.ac.uk/pdbsum/6tqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqk ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
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| [[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.
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| == Function ==
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| [[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]
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Assembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization, and antibacterial defense is driven by a ubiquitous polymerization module known as zona pellucida (ZP) "domain". Despite the conservation of this element from hydra to humans, no detailed information is available on the filamentous conformation of any ZP module protein. Here, we report a cryo-electron microscopy study of uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant protein in human urine and an archetypal ZP module-containing molecule, in its mature homopolymeric state. UMOD forms a one-start helix with an unprecedented 180-degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD-based models of heteromeric vertebrate egg coat filaments identify a common sperm-binding region at the interface between subunits.
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| Cryo-EM structure of native human uromodulin, a zona pellucida module polymer.,Stsiapanava A, Xu C, Brunati M, Zamora-Caballero S, Schaeffer C, Bokhove M, Han L, Hebert H, Carroni M, Yasumasu S, Rampoldi L, Wu B, Jovine L EMBO J. 2020 Nov 16:e106807. doi: 10.15252/embj.2020106807. PMID:33196145<ref>PMID:33196145</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6tqk" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Carroni, M]] | | [[Category: Carroni M]] |
| [[Category: Jovine, L]] | | [[Category: Jovine L]] |
| [[Category: Stsiapanava, A]] | | [[Category: Stsiapanava A]] |
| [[Category: Wu, B]] | | [[Category: Wu B]] |
| [[Category: Xu, C]] | | [[Category: Xu C]] |
| [[Category: Egf domain]]
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| [[Category: Extracellular matrix]]
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| [[Category: Glycoprotein]]
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| [[Category: Interdomain linker]]
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| [[Category: N-glycan]]
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| [[Category: Protein filament]]
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| [[Category: Protein polymerization]]
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| [[Category: Structural protein]]
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| [[Category: Zp domain]]
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| [[Category: Zp module]]
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| [[Category: Zp-c domain]]
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| [[Category: Zp-n domain]]
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