5jr4
Crystal structure of FimH A27V/V163A from E. coli UTI89 bound to FimG N-terminal extensionCrystal structure of FimH A27V/V163A from E. coli UTI89 bound to FimG N-terminal extension
Structural highlights
FunctionPublication Abstract from PubMedPositive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state-mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved "moderate" affinity to optimize persistence in the bladder during UTI. Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions.,Kalas V, Pinkner JS, Hannan TJ, Hibbing ME, Dodson KW, Holehouse AS, Zhang H, Tolia NH, Gross ML, Pappu RV, Janetka J, Hultgren SJ Sci Adv. 2017 Feb 10;3(2):e1601944. doi: 10.1126/sciadv.1601944. eCollection 2017, Feb. PMID:28246638[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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