Free-flowing filaments of Uromodulin protect against urinary tract infections (UTIs) by duping potentially harmful bacteria to attach to their fishbone-like molecular architecture - rather than to sensitive urinary tract tissues - before being flushed out of the body during urination, researchers report. The results of this new study provide a framework for understanding how the common urinary glycoprotein Uromodulin (Umod) protects against human UTIs, and also provide insights into its other, more enigmatic physiological functions. Umod is the most abundant urinary protein and forms filaments known to help defend against invading bacterial uropathogens that cause urinary tract infections - one of the most painfully common bacterial infections in humans. However, despite being a common component in urine and having recognized roles in human health and disease, the molecular architecture and function of Umod filaments in urine isn't well understood. In this study, Gregor Weiss and colleagues used cryo-electron tomography (cryo-ET) to produce detailed, high-resolution and three-dimensional molecular views of Umod filaments, revealing their zigzagging shape. According to Weiss et al., Umod proteins form stacked fishbone-like filaments, characterized by regularly spaced "arms" protruding from a central "backbone" filament. These multi-valent molecules act as a kind of decoy - offering bacterial pathogens a myriad of attractive places to attach to the free-floating filaments instead of the tissues lining the urinary tract. In this way, harmful uropathogens are collected by Umod filaments and evacuated alongside urine. According to the authors, the findings serve as a starting point to understanding the mechanism underlying Umod's other roles in salt transport, kidney disease and innate immunity.
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Journal
Science