Evidence map›Paper›PMID 32815518›Full record

ArticleeLife2020

The cryo-EM structure of the human uromodulin filament core reveals a unique assembly mechanism.

Jessica J Stanisich, Dawid S Zyla, Pavel Afanasyev, Jingwei Xu, Anne Kipp, Eric Olinger, Olivier Devuyst, Martin Pilhofer, Daniel Boehringer, Rudi Glockshuber

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
7.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Uromodulin and the study of urinary extracellular vesicles.Journal of extracellular biology · 2024
    Review
  8. Article
  9. Uromodulin biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. UMOD and the architecture of kidney disease.Pflugers Archiv : European journal of physiology · 2022
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Jessica J Stanisich *Institute of Molecular Biology & Biophysics, ETH Zurich, Zurich, Switzerland.ORCID 0000-0002-2702-8092
Dawid S Zyla *Institute of Molecular Biology & Biophysics, ETH Zurich, Zurich, Switzerland.ORCID 0000-0001-8471-469X
Pavel AfanasyevCryo-​EM Knowledge Hub (CEMK), ETH Zurich, Zurich, Switzerland.ORCID 0000-0002-6353-6895
Jingwei XuInstitute of Molecular Biology & Biophysics, ETH Zurich, Zurich, Switzerland.
Anne KippInstitute of Physiology, University of Zurich, Zurich, Switzerland.
Eric OlingerTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, United Kingdom.ORCID 0000-0003-1178-7980
Olivier DevuystInstitute of Physiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-3744-4767
Martin PilhoferInstitute of Molecular Biology & Biophysics, ETH Zurich, Zurich, Switzerland.ORCID 0000-0002-3649-3340
Daniel BoehringerCryo-​EM Knowledge Hub (CEMK), ETH Zurich, Zurich, Switzerland.
Rudi GlockshuberInstitute of Molecular Biology & Biophysics, ETH Zurich, Zurich, Switzerland.ORCID 0000-0003-3320-3843
ETH Zurich · CHUniversity of Zurich · CHNewcastle University · GB

Funding

H2020 European Research Council 679209NOMIS Stiftung n/aSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_189044Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030B_176403/1Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 31003A_156304Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 31003A_179255Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung P2ZHP3_195181Swiss National Centre of Competence in Research Kidney Control of Homeostasis n/a
6 · The paper itself

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.

Indexed as

UromodulinCryoelectron MicroscopyHumansModels, MolecularPolymerizationProtein Conformation, beta-StrandProtein DomainsUMOD protein, humanUromodulincryo-EMglycoproteinhumanimmunoglobulin-like foldmolecular biophysicsstructural biologyuromodulinzona pellucida module

Identifiers

PMID32815518
PMCPMC7486124
OpenAlexW3079536796

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.