ArticleeLife2020
The cryo-EM structure of the human uromodulin filament core reveals a unique assembly mechanism.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Comparative mass spectrometry analysis of high and low centrifugation extracellular vesicle (EV) pellets from healthy urine following Tamm-Horsfall protein removal.Clinical proteomics · 2026Article
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- Structure of human glycoprotein 2 reveals mechanisms underlying filament formation and adaption to proteolytic environment in the digestive tract.PLoS biology · 2025Article
- Microvilli control the morphogenesis of the tectorial membrane extracellular matrix.Developmental cell · 2025Article
- Identification of Six Novel Proteins Containing a ZP Module from Nemertean Species.Biomolecules · 2024Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Uromodulin and the study of urinary extracellular vesicles.Journal of extracellular biology · 2024Review
- Apical cell expansion maintained by Dusky-like establishes a scaffold for corneal lens morphogenesis.Science advances · 2024Article
- Uromodulin biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective.Kidney diseases (Basel, Switzerland) · 2024Review
- Article
- Concentration strategies for spiked and naturally present biomarkers in non-invasively collected first-void urine.European journal of medical research · 2024Article
- Microvilli regulate the release modes of alpha-tectorin to organize the domain-specific matrix architecture of the tectorial membrane.bioRxiv : the preprint server for biology · 2024Article
- The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024Review
- Donor-strand exchange drives assembly of the TasA scaffold in Bacillus subtilis biofilms.Nature communications · 2022Article
- Zona Pellucida like Domain Protein 1 (ZPLD1) Polymerization Is Regulated by Two Distinguished Hydrophobic Motifs.International journal of molecular sciences · 2022Article
- Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms.Hypertension (Dallas, Tex. : 1979) · 2022Review
- UMOD and the architecture of kidney disease.Pflugers Archiv : European journal of physiology · 2022Review
- Better, Faster, Cheaper: Recent Advances in Cryo-Electron Microscopy.Annual review of biochemistry · 2022Review
- The kidney releases a nonpolymerizing form of uromodulin in the urine and circulation that retains the external hydrophobic patch domain.American journal of physiology. Renal physiology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The glycoprotein uromodulin (UMOD) is the most abundant protein in human urine and forms filamentous homopolymers that encapsulate and aggregate uropathogens, promoting pathogen clearance by urine excretion. Despite its critical role in the innate immune response against urinary tract infections, the structural basis and mechanism of UMOD polymerization remained unknown. Here, we present the cryo-EM structure of the UMOD filament core at 3.5 Å resolution, comprised of the bipartite zona pellucida (ZP) module in a helical arrangement with a rise of ~65 Å and a twist of ~180°. The immunoglobulin-like ZPN and ZPC subdomains of each monomer are separated by a long linker that interacts with the preceding ZPC and following ZPN subdomains by β-sheet complementation. The unique filament architecture suggests an assembly mechanism in which subunit incorporation could be synchronized with proteolytic cleavage of the C-terminal pro-peptide that anchors assembly-incompetent UMOD precursors to the membrane.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.