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TitleArchitecture and function of human uromodulin filaments in urinary tract infections.
Journal, issue, pagesScience, Vol. 369, Issue 6506, Page 1005-1010, Year 2020
Publish dateAug 21, 2020
AuthorsGregor L Weiss / Jessica J Stanisich / Maximilian M Sauer / Chia-Wei Lin / Jonathan Eras / Dawid S Zyla / Johannes Trück / Olivier Devuyst / Markus Aebi / Martin Pilhofer / Rudi Glockshuber /
PubMed AbstractUromodulin is the most abundant protein in human urine, and it forms filaments that antagonize the adhesion of uropathogens; however, the filament structure and mechanism of protection remain poorly ...Uromodulin is the most abundant protein in human urine, and it forms filaments that antagonize the adhesion of uropathogens; however, the filament structure and mechanism of protection remain poorly understood. We used cryo-electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that uromodulin acts as a multivalent ligand for the bacterial type 1 pilus adhesin, presenting specific epitopes on the regularly spaced arms. Imaging of uromodulin-uropathogen interactions in vitro and in patient urine showed that uromodulin filaments associate with uropathogens and mediate bacterial aggregation, which likely prevents adhesion and allows clearance by micturition. These results provide a framework for understanding uromodulin in urinary tract infections and in its more enigmatic roles in physiology and disease.
External linksScience / PubMed:32616672
MethodsEM (tomography) / EM (subtomogram averaging)
Resolution15.6 - 17.3 Å
Structure data

EMDB-11128:
Cryo-electron tomogram of human Uromodulin filaments
Method: EM (tomography)

EMDB-11129:
Subtomogram average of human Uromodulin filaments
Method: EM (subtomogram averaging) / Resolution: 15.6 Å

EMDB-11130:
Cryo-electron tomogram of elastase treated human Uromodulin filaments (eUmod)
Method: EM (tomography)

EMDB-11131:
Subtomogram average of elastase treated human Uromodulin filaments (eUmod)
Method: EM (subtomogram averaging) / Resolution: 17.3 Å

EMDB-11132:
Cryo-electron tomogram of human Uromodulin filaments incubated with FimH lectin domain
Method: EM (tomography)

EMDB-11133:
Subtomogram average of human Uromodulin filaments incubated with FimH lectin domain
Method: EM (subtomogram averaging) / Resolution: 16.6 Å

EMDB-11134:
Cryo-electron tomogram of elastase treated human Uromodulin filaments incubated with FimH lectin domain
Method: EM (tomography)

EMDB-11135:
Subtomogram average of elastase treated human Uromodulin fibers incubated with FimH lectin domain
Method: EM (subtomogram averaging) / Resolution: 15.9 Å

EMDB-11136:
Cryo-electron tomogram of E. coli AAEC [pSH2] incubated with human Uromodulin filaments
Method: EM (tomography)

EMDB-11137:
Cryo-electron tomogram of non-piliated E. coli AAEC189 incubated with human Uromodulin filaments
Method: EM (tomography)

EMDB-11138:
Cryo-electron tomogram of FIB milled E.coli - Uromodulin aggregates
Method: EM (tomography)

EMDB-11139:
Cryo-electron tomogram of E. coli AAEC189 [pSH2] incubated with elastase treated human Uromodulin filaments
Method: EM (tomography)

EMDB-11140:
Cryo-electron tomogram of urine from patient with E. coli urinary tract infection
Method: EM (tomography)

EMDB-11141:
Cryo-electron tomogram of urine from patient with K. pneumoniae urinary tract infection
Method: EM (tomography)

EMDB-11142:
Cryo-electron tomogram of urine from patient with P. aeruginosa urinary tract infection
Method: EM (tomography)

EMDB-11143:
Cryo-electron tomogram of urine from patient with S. mitis urinary tract infection
Method: EM (tomography)

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  • Homo sapiens (human)

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