6Y4F

X-ray structure of the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH

Summary for 6Y4F

• Entry DOI: 10.2210/pdb6y4f/pdb
• Related: 6Y4E
• Descriptor: Fimbrial adhesin, ZINC ION, GLUTAMIC ACID, ... (4 entities in total)
• Functional Keywords: metal binding protein, adhesin, cell adhesion
• Biological source: Proteus mirabilis (strain HI4320)
• Total number of polymer chains: 1
• Total formula weight: 15762.98

Authors

Knight, S.D.,Ubhayasekera, W.,Jiang, W. (deposition date: 2020-02-20, release date: 2020-08-19, Last modification date: 2024-10-23)

Primary citation

Jiang, W.,Ubhayasekera, W.,Breed, M.C.,Norsworthy, A.N.,Serr, N.,Mobley, H.L.T.,Pearson, M.M.,Knight, S.D.
MrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation.
Plos Pathog., 16:e1008707-e1008707, 2020

PubMed Abstract: Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor.

PubMed: 32780778
DOI: 10.1371/journal.ppat.1008707

Experimental method

X-RAY DIFFRACTION (1.75 Å)