RT Journal Article
SR Electronic
T1 Cryo-EM Structure of Native Human Uromodulin, a Zona Pellucida Module Polymer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.28.119206
DO 10.1101/2020.05.28.119206
A1 Alena Stsiapanava
A1 Chenrui Xu
A1 Martina Brunati
A1 Sara Zamora-Caballero
A1 Céline Schaeffer
A1 Ling Han
A1 Marta Carroni
A1 Shigeki Yasumasu
A1 Luca Rampoldi
A1 Bin Wu
A1 Luca Jovine
YR 2020
UL http://biorxiv.org/content/early/2020/05/28/2020.05.28.119206.abstract
AB 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 human, no information is available on the filamentous conformation of any ZP module protein. Here we report the cryo-electron microscopy structure 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 mammalian and avian heteromeric egg coat filaments identify a common sperm-binding region at the interface between subunits.Competing Interest StatementThe authors have declared no competing interest.