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

Autor: 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
Přispěvatelé: Stsiapanava, A, Xu, C, Brunati, M, Schaeffer, C, Zamora-Caballero, S, Algarra, B, Han, L, Carroni, M, Yasumasu, S, Rampoldi, L, Wu, B, Jovine, L
Jazyk: angličtina
Rok vydání: 2020
Předmět:
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
Zdroj: The EMBO Journal
ISSN: 1460-2075
0261-4189
Popis: 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.
Databáze: OpenAIRE
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