Cryo‐EM structure of native human uromodulin, a zona pellucida module polymer

Abstract: 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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Cryo‐EM structure of native human uromodulin, a zona pellucida module polymer ; volume:39 ; number:24 ; year:2020 ; extent:20
The EMBO journal / European Molecular Biology Organization ; 39, Heft 24 (2020) (gesamt 20)

Creator
Stsiapanava, Alena
Xu, Chenrui
Brunati, Martina
Zamora‐Caballero, Sara
Schaeffer, Céline
Bokhove, Marcel
Han, Ling
Hebert, Hans
Carroni, Marta
Yasumasu, Shigeki
Rampoldi, Luca
Wu, Bin
Jovine, Luca

DOI
10.15252/embj.2020106807
URN
urn:nbn:de:101:1-2022062807585597313431
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:27 AM CEST

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Associated

  • Stsiapanava, Alena
  • Xu, Chenrui
  • Brunati, Martina
  • Zamora‐Caballero, Sara
  • Schaeffer, Céline
  • Bokhove, Marcel
  • Han, Ling
  • Hebert, Hans
  • Carroni, Marta
  • Yasumasu, Shigeki
  • Rampoldi, Luca
  • Wu, Bin
  • Jovine, Luca

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