6TQK

Cryo-EM of native human uromodulin (UMOD)/Tamm-Horsfall protein (THP) filament.

Summary for 6TQK

• Entry DOI: 10.2210/pdb6tqk/pdb
• Related: 3NK4 4WRN 6TQL
• EMDB information: 10553 10554
• Descriptor: Uromodulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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)
• Functional Keywords: zp module, zp domain, zp-n domain, zp-c domain, interdomain linker, egf domain, extracellular matrix, glycoprotein, n-glycan, structural protein, protein filament, protein polymerization
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 188746.36

Authors

Stsiapanava, A.,Xu, C.,Carroni, M.,Wu, B.,Jovine, L. (deposition date: 2019-12-16, release date: 2020-11-04, Last modification date: 2024-10-09)

Primary citation

Stsiapanava, A.,Xu, C.,Brunati, M.,Zamora-Caballero, S.,Schaeffer, C.,Bokhove, M.,Han, L.,Hebert, H.,Carroni, M.,Yasumasu, S.,Rampoldi, L.,Wu, B.,Jovine, L.
Cryo-EM structure of native human uromodulin, a zona pellucida module polymer.
Embo J., 39:e106807-e106807, 2020

PubMed 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.

PubMed: 33196145
DOI: 10.15252/embj.2020106807

Experimental method

ELECTRON MICROSCOPY (3.35 Å)