9NU3

Uromodulin filament lattice in the kinked arrangement from human urine

9NU3 の概要

• エントリーDOI: 10.2210/pdb9nu3/pdb
• EMDBエントリー: 49794
• 分子名称: Uromodulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: kidney, urine, uropathogen, filament, lattice, antimicrobial protein, kidney disease, uti, urinary tract infection, infection
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 1281181.92

構造登録者

Chang, A.N.,Fitzpatrick, A.W.P. (登録日: 2025-03-19, 公開日: 2025-05-21)

主引用文献

Chang, A.N.,Cerutti, G.,Ogawa, Y.,Basler, A.,Switzer, W.,Eng-Kohn, M.,Lee, C.,Fitzpatrick, A.W.P.
Structural basis of human uromodulin filament networks in uropathogen capture.
Structure, 2025

PubMed Abstract: Uromodulin (UMOD), the most abundant protein in human urine, is essential for kidney function and urinary tract health. UMOD forms filaments that bind to uropathogenic bacteria, facilitating their aggregation and clearance from the urinary tract. Here, we present the cryo-electron microscopy (cryo-EM) structure of the bacteria-binding D10C domain of UMOD and reveal its binding to the filament core. The details of D10C-core binding explain the formation of distinct filament lattice architectures adopted by UMOD. The D10C-core binding interface gives rise to diverse filament lattice structures, ranging from open and expansive to compact and dense conformations, or a combination of both. We hypothesize that other molecules present in urine may act as cross-linking agents, further stabilizing this binding interface and facilitating the connection of individual filaments into larger networks capable of effectively trapping bacteria. Structural mapping of kidney disease-related mutations points toward the abolition of disulfide bonds and promotion of mutant UMOD aggregation.

PubMed: 40345203
DOI: 10.1016/j.str.2025.04.011

実験手法

ELECTRON MICROSCOPY (5 Å)