1. Cryo‐EM structure of native human uromodulin, a zona pellucida module polymer
- Author
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Chenrui Xu, Hans Hebert, Marta Carroni, Ling Han, Céline Schaeffer, Martina Brunati, Alena Stsiapanava, Shigeki Yasumasu, Marcel Bokhove, Luca Jovine, Sara Zamora-Caballero, Bin Wu, Luca Rampoldi, Stsiapanava, A, Xu, C, Brunati, M, Schaeffer, C, Zamora-Caballero, S, Algarra, B, Han, L, Carroni, M, Yasumasu, S, Rampoldi, L, Wu, B, and Jovine, L
- Subjects
cryo‐electron microscopy ,Tamm–Horsfall protein ,Cryo-electron microscopy ,uromodulin ,Polymers ,Protein Conformation ,zona pellucida ,Morphogenesis ,Urogenital System ,General Biochemistry, Genetics and Molecular Biology ,Article ,Polymerization ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,Structural Biology ,medicine ,Extracellular ,Animals ,Humans ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,Binding site ,Zona pellucida ,Protein precursor ,Molecular Biology ,ZP domain ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,General Immunology and Microbiology ,biology ,General Neuroscience ,Cryoelectron Microscopy ,Polymer ,Articles ,Microbiology, Virology & Host Pathogen Interaction ,Cell biology ,medicine.anatomical_structure ,chemistry ,biology.protein ,Female ,030217 neurology & neurosurgery - 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., Insights into the architecture of uromodulin filaments involved in the capture of uropathogenic bacteria, and structurally‐related vertebrate egg coat material, suggest how a widespread extracellular polymerization module can support multiple functions.
- Published
- 2020