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Structure paper

TitleStructure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH.
Journal, issue, pagesNat Struct Mol Biol, Vol. 29, Issue 3, Page 190-193, Year 2022
Publish dateMar 10, 2022
AuthorsAlena Stsiapanava / Chenrui Xu / Shunsuke Nishio / Ling Han / Nao Yamakawa / Marta Carroni / Kathryn Tunyasuvunakool / John Jumper / Daniele de Sanctis / Bin Wu / Luca Jovine /
PubMed AbstractGlycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 ...Glycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 predictions with X-ray crystallography and cryo-EM, we show that these proteins contain a bipartite decoy module whose new fold presents the high-mannose glycan recognized by FimH. The structure rationalizes UMOD mutations associated with kidney diseases and visualizes a key epitope implicated in cast nephropathy.
External linksNat Struct Mol Biol / PubMed:35273390 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.35 - 7.4 Å
Structure data

13378

7pfp

EMDB-13378, PDB-7pfp:
Full-length cryo-EM structure of the native human uromodulin (UMOD)/Tamm-Horsfall protein (THP) filament
Method: EM (single particle) / Resolution: 6.1 Å

13794

7q3n

EMDB-13794, PDB-7q3n:
Cryo-EM of the complex between human uromodulin (UMOD)/Tamm-Horsfall protein (THP) and the FimH lectin domain from uropathogenic E. coli
Method: EM (single particle) / Resolution: 7.4 Å

PDB-7p6r:
Crystal structure of the FimH-binding decoy module of human glycoprotein 2 (GP2) (crystal form I)
Method: X-RAY DIFFRACTION / Resolution: 1.9 Å

PDB-7p6s:
Crystal structure of the FimH-binding decoy module of human glycoprotein 2 (GP2) (crystal form II)
Method: X-RAY DIFFRACTION / Resolution: 1.35 Å

PDB-7p6t:
Crystal structure of the FimH-binding decoy module of human glycoprotein 2 (GP2) (crystal form III)
Method: X-RAY DIFFRACTION / Resolution: 1.4 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-HOH:
WATER

ChemComp-9JE:
pentane-1,5-diol

ChemComp-9D2:
2-ethyl-2-(hydroxymethyl)propane-1,3-diol

Source
  • homo sapiens (human)
  • escherichia coli (strain uti89 / upec) (bacteria)
KeywordsANTIMICROBIAL PROTEIN / Extracellular matrix / glycoprotein / N-glycan / structural protein / decoy module / D10C domain / D8C sequence / pancreas / intestine / mucosal immunity / FimH / AlphaFold / EGF DOMAIN / BETA-HAIRPIN / ZP MODULE / ZP DOMAIN / ZP-N DOMAIN / ZP-C DOMAIN / INTERDOMAIN LINKER / PROTEIN FILAMENT / PROTEIN POLYMERIZATION / D8C DOMAIN / HIGH-MANNOSE SUGAR / CELL ADHESION / BACTERIAL ADHESIN / TYPE I PILUS / SUGAR BINDING PROTEIN / LECTIN / URINARY TRACT INFECTION / UTI / UROPATHOGENIC E. COLI / UPEC

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