瑞士苏黎世联邦理工学院Martin Pilhofer团队解析出尿路感染时人类尿调节素细丝的结构。该研究于2020年7月2日在线发表于《科学》。

Title: Architecture and function of human uromodulin filaments in urinary tract infections

Author: Gregor L. Weiss, Jessica J. Stanisich, Maximilian M. Sauer, Chia-Wei Lin, Jonathan Eras, Dawid S. Zyla, Johannes Trück, Olivier Devuyst, Markus Aebi, Martin Pilhofer, Rudi Glockshuber

Issue&Volume: 2020/07/02

Abstract: Abstract Uromodulin is the most abundant protein in human urine and forms filaments that antagonize the adhesion of uropathogens; however, filament structure and mechanism of protection remain poorly understood. We used cryo-electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that uromodulin acts as a multivalent ligand for the bacterial type 1 pilus adhesin, presenting specific epitopes on the regularly spaced arms. Imaging of uromodulin-uropathogen interactions in vitro and in patient urine showed that uromodulin filaments associate with uropathogens and mediate bacterial aggregation, which likely prevents adhesion and allows clearance by micturition. These results provide a framework for understanding uromodulin in urinary tract infections and in its more enigmatic roles in physiology and disease.

DOI: 10.1126/science.aaz9866

Source: https://science.sciencemag.org/content/early/2020/07/01/science.aaz9866