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J Mol Biol. 2009 Sep 18;392(2):352-61. doi: 10.1016/j.jmb.2009.06.077. Epub 2009 Jul 3.

Uropathogenic E. coli adhesin-induced host cell receptor conformational changes: implications in transmembrane signaling transduction.

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1
Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.

Abstract

Urinary tract infection is the second most common infectious disease and is caused predominantly by type 1-fimbriated uropathogenic Escherichia coli (UPEC). UPEC initiates infection by attaching to uroplakin (UP) Ia, its urothelial surface receptor, via the FimH adhesins capping the distal end of its fimbriae. UP Ia, together with UP Ib, UP II, and UP IIIa, forms a 16-nm receptor complex that is assembled into hexagonally packed, two-dimensional crystals (urothelial plaques) covering >90% of the urothelial apical surface. Recent studies indicate that FimH is the invasin of UPEC as its attachment to the urothelial surface can induce cellular signaling events including calcium elevation and the phosphorylation of the UP IIIa cytoplasmic tail, leading to cytoskeletal rearrangements and bacterial invasion. However, it remains unknown how the binding of FimH to the UP receptor triggers a signal that can be transmitted through the highly impermeable urothelial apical membrane. We show here by cryo-electron microscopy that FimH binding to the extracellular domain of UP Ia induces global conformational changes in the entire UP receptor complex, including a coordinated movement of the tightly bundled transmembrane helices. This movement of the transmembrane helix bundles can cause a corresponding lateral translocation of the UP cytoplasmic tails, which can be sufficient to trigger downstream signaling events. Our results suggest a novel pathogen-induced transmembrane signal transduction mechanism that plays a key role in the initial stages of UPEC invasion and receptor-mediated bacterial invasion in general.

PMID:
19577575
PMCID:
PMC2755582
DOI:
10.1016/j.jmb.2009.06.077
[Indexed for MEDLINE]
Free PMC Article
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