Structural Basis of the Interaction of the Pyelonephritic E. coli Adhesin to Its Human Kidney Receptor

Dodson, Karen W.; Pinkner, Jerome S.; Rose, Thierry; Magnusson, Göran; Hultgren, Scott J.; Waksman, Gabriel

doi:10.1016/s0092-8674(01)00388-9

Cited by 236 publications

(231 citation statements)

References 44 publications

(5 reference statements)

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“…The solved three-dimensional crystal structure of E. coli PapG has provided a view of the molecular mechanisms of the tropism of E. coli toward uroepithelium in the human kidney (42). The Gal␣1-4Gal-specific adhesion of S. suis represents an example where galabiose analogs or polyvalent dendrimers have been shown to be exceptionally efficient inhibitors at nanomolar concentrations (22,43,44); however, the identity and structure of the adhesin have remained elusive.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-α1–4-galactose-containing Glycoconjugates

Kouki

Haataja

Loimaranta

et al. 2011

Journal of Biological Chemistry

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Background: Adhesion is a prerequisite to infectious diseases. Results: A novel streptococcal Gal␣1-4Gal-recognizing adhesin was identified, which has no homology to known Gal␣1-4Gal-recognizing proteins. Conclusion: SadP is an example of convergent evolution of adhesins to binding to the same receptor, Gal␣1-4Gal, abundant in glycolipids. Significance: Identification of SadP helps to understand the molecular basis of streptococcal pathogenicity.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-α1–4-galactose-containing Glycoconjugates

Kouki

Haataja

Loimaranta

et al. 2011

Journal of Biological Chemistry

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“…The P pilus comprises a flexible-tip fibrillum made up of minor pilins with the two-domain adhesin PapG at the distal end where it can recognize Galα1-4Gal disaccharide-containing glycolipids found in the human kidney (14,15). The P pilus tip is joined to a righthanded, helical pilus rod made up of PapA pilins (16,17) and is anchored in the OM via the terminator/anchoring subunit PapH (18).…”

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confidence: 99%

Molecular basis of usher pore gating in Escherichia coli pilus biogenesis

Volkan

Kalas

Pinkner³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Extracellular fibers called chaperone-usher pathway pili are critical virulence factors in a wide range of Gram-negative pathogenic bacteria that facilitate binding and invasion into host tissues and mediate biofilm formation. Chaperone-usher pathway ushers, which catalyze pilus assembly, contain five functional domains: a 24-stranded transmembrane β-barrel translocation domain (TD), a β-sandwich plug domain (PLUG), an N-terminal periplasmic domain, and two Cterminal periplasmic domains (CTD1 and 2). Pore gating occurs by a mechanism whereby the PLUG resides stably within the TD pore when the usher is inactive and then upon activation is translocated into the periplasmic space, where it functions in pilus assembly. Using antibiotic sensitivity and electrophysiology experiments, a single salt bridge was shown to function in maintaining the PLUG in the TD channel of the P pilus usher PapC, and a loop between the 12th and 13th beta strands of the TD (β12-13 loop) was found to facilitate pore opening. Mutation of the β12-13 loop resulted in a closed PapC pore, which was unable to efficiently mediate pilus assembly. Deletion of the PapH terminator/anchor resulted in increased OM permeability, suggesting a role for the proper anchoring of pili in retaining OM integrity. Further, we introduced cysteine residues in the PLUG and N-terminal periplasmic domains that resulted in a FimD usher with a greater propensity to exist in an open conformation, resulting in increased OM permeability but no loss in type 1 pilus assembly. These studies provide insights into the molecular basis of usher pore gating and its roles in pilus biogenesis and OM permeability.outer membrane usher | macromolecular assembly | bacterial pathogenesis

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“…Upon their transfer to the periplasm (10), these structural subunits are assembled through the actions of the periplasmic chaperone (PapD) and the integral outer membrane usher (PapC) in a specific order into bipartite P pilus fibers composing an open helical tip fibrillum made up of (from the tip) PapG (11), PapF, multiple PapEs, and PapK (12,13), connected to a right-handed helical rod made up of thousands of copies of PapA (14)(15)(16)(17) and terminated by a single copy of PapH (18,19). Each pilin Ig fold is missing the seventh C-terminal β-strand of the canonical Ig fold.…”

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confidence: 99%

Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine

Volkan¹,

Ford

Pinkner³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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P pili are prototypical chaperone-usher pathway-assembled pili used by Gram-negative bacteria to adhere to host tissues. The PapC usher contains five functional domains: a transmembrane β-barrel, a β-sandwich Plug, an N-terminal (periplasmic) domain (NTD), and two C-terminal (periplasmic) domains, CTD1 and CTD2. Here, we delineated usher domain interactions between themselves and with chaperone-subunit complexes and showed that overexpression of individual usher domains inhibits pilus assembly. Prior work revealed that the Plug domain occludes the pore of the transmembrane domain of a solitary usher, but the chaperone-adhesinbound usher has its Plug displaced from the pore, adjacent to the NTD. We demonstrate an interaction between the NTD and Plug domains that suggests a biophysical basis for usher gating. Furthermore, we found that the NTD exhibits high-affinity binding to the chaperone-adhesin (PapDG) complex and low-affinity binding to the major tip subunit PapE (PapDE). We also demonstrate that CTD2 binds with lower affinity to all tested chaperone-subunit complexes except for the chaperone-terminator subunit (PapDH) and has a catalytic role in dissociating the NTD-PapDG complex, suggesting an interplay between recruitment to the NTD and transfer to CTD2 during pilus initiation. The Plug domain and the NTDPlug complex bound all of the chaperone-subunit complexes tested including PapDH, suggesting that the Plug actively recruits chaperone-subunit complexes to the usher and is the sole recruiter of PapDH. Overall, our studies reveal the cooperative, active roles played by periplasmic domains of the usher to initiate, grow, and terminate a prototypical chaperone-usher pathway pilus.biolayer interferometry | macromolecular assembly | urinary tract infections | virulence factor | bacterial pathogenesis

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Structural Basis of the Interaction of the Pyelonephritic E. coli Adhesin to Its Human Kidney Receptor

Cited by 236 publications

References 44 publications

Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-α1–4-galactose-containing Glycoconjugates

Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-α1–4-galactose-containing Glycoconjugates

Molecular basis of usher pore gating in Escherichia coli pilus biogenesis

Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine

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