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天然人尿调节素的冷冻电镜结构，一种透明带模块聚合物。

Cryo-EM structure of native human uromodulin, a zona pellucida module polymer.

机构信息

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

出版信息

EMBO J. 2020 Dec 15;39(24):e106807. doi: 10.15252/embj.2020106807. Epub 2020 Nov 16.

DOI:10.15252/embj.2020106807
PMID:33196145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7737619/
Abstract

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 humans, no detailed information is available on the filamentous conformation of any ZP module protein. Here, we report a cryo-electron microscopy study 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 heteromeric vertebrate egg coat filaments identify a common sperm-binding region at the interface between subunits.

摘要

介导形态发生、听力、受精和抗菌防御等基本生物学过程的细胞外丝和基质的组装由一种普遍存在的聚合模块驱动，称为透明带（ZP）“结构域”。尽管从水螅到人，这个元素都得到了保守，但任何 ZP 模块蛋白的丝状构象都没有详细的信息。在这里，我们报告了对尿调蛋白（UMOD）/Tamm-Horsfall 蛋白的冷冻电镜研究，UMOD 是人尿中最丰富的蛋白质，也是典型的 ZP 模块包含分子，处于其成熟的同源聚合状态。UMOD 形成一个单启动螺旋，亚基之间的扭转角度为 180 度，这是前所未有的，亚基被结构域间连接子包裹，这些连接子由于前肽解离而完全重组。尿液中丝状纤维的侧向相互作用产生了暴露结合位点棋盘的薄片，以捕获尿路致病性细菌，并且基于 UMOD 的脊椎动物卵壳纤维异源二聚体模型确定了亚基界面处的一个共同的精子结合区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/eda7eb221bf5/EMBJ-39-e106807-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/fff78961e671/EMBJ-39-e106807-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/e0c06e1e4af4/EMBJ-39-e106807-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/92cee6e50850/EMBJ-39-e106807-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/99a1df610767/EMBJ-39-e106807-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/3f2a82a0a1a0/EMBJ-39-e106807-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/fd78c6ee77ff/EMBJ-39-e106807-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/0f84d0c44bc0/EMBJ-39-e106807-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/e23932957466/EMBJ-39-e106807-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/583dc519cb25/EMBJ-39-e106807-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/2a1f8d770456/EMBJ-39-e106807-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/03e906653f17/EMBJ-39-e106807-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/eda7eb221bf5/EMBJ-39-e106807-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/fff78961e671/EMBJ-39-e106807-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/e0c06e1e4af4/EMBJ-39-e106807-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/92cee6e50850/EMBJ-39-e106807-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/99a1df610767/EMBJ-39-e106807-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/3f2a82a0a1a0/EMBJ-39-e106807-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/fd78c6ee77ff/EMBJ-39-e106807-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/0f84d0c44bc0/EMBJ-39-e106807-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/e23932957466/EMBJ-39-e106807-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/583dc519cb25/EMBJ-39-e106807-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/2a1f8d770456/EMBJ-39-e106807-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/03e906653f17/EMBJ-39-e106807-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d22/7737619/eda7eb221bf5/EMBJ-39-e106807-g013.jpg

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