A structured interdomain linker directs self-polymerization of human uromodulin

• Urinary tract infection is the most common nonepidemic bacterial infection in humans, with 150 million cases per year and a global health care cost above $6 billion. Because the urinary tract is not protected by mucus, mammals produce a molecular net that captures pathogenic bacteria in the urine and clears them from the body. By visualizing the 3D structure of its building block, glycoprotein uromodulin, we provide insights into how the net is built, and how it is compromised by mutations in patients with kidney diseases. Our work also explains nonsyndromic deafness due to mutations affecting the tectorial membrane, a similar filamentous structure in the human inner ear.

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