9bog
Structural basis for adhesin secretion by the outer-membrane usher in type 1 pili
Structural highlights
FunctionFIMD_ECOLI Involved in the export and assembly of FimA fimbrial subunits across the outer membrane. Publication Abstract from PubMedGram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary tip complex in the type 1 pilus system from Escherichia coli, which consists of the usher FimD, chaperone FimC, adhesin FimH, and the tip adapter FimF. In this structure, the usher FimD is caught in the act of secreting its cognate adhesin FimH. Comparison with previous structures depicting the adhesin either first entering or having completely exited the usher pore reveals remarkable structural plasticity of the two-domain adhesin during translocation. Moreover, a piliation assay demonstrated that the structural plasticity, enabled by a flexible linker between the two domains, is a prerequisite for adhesin translocation through the usher pore and thus pilus biogenesis. Overall, this study provides molecular details of adhesin translocation across the outer membrane and elucidates a unique conformational state adopted by the adhesin during stepwise secretion through the usher pore. This study elucidates fundamental aspects of FimH and usher dynamics critical in urinary tract infections and is leading to antibiotic-sparing therapeutics. Structural basis for adhesin secretion by the outer-membrane usher in type 1 pili.,Bitter RM, Zimmerman MI, Summers BT, Pinkner JS, Dodson KW, Hultgren SJ, Yuan P Proc Natl Acad Sci U S A. 2024 Oct;121(40):e2410594121. doi: , 10.1073/pnas.2410594121. Epub 2024 Sep 24. PMID:39316053[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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