The Yeh pilus adhesin is equipped with an α-helical flap motif, which contributes to pectin adherence

The Yeh chaperone-usher pathway (CUP) pilus adhesin is encoded in one-half of all <i>Escherichia coli</i>. Yet little is known about its structure and function in <i>E. coli</i> persistence and pathogenesis. Structural investigations reveal that the adhesin receptor binding domains (RBDs) of YehD and its relative YhlD both share a canonical β-rich core and an α-helical flap motif that is hinged at the distal end of the core. This flap was observed in both open and closed conformations using molecular dynamics simulations. The closed conformation is dependent on a hydrophobic patch of amino acids on the distal end of the flap. Functionally, YehD<sub>RBD</sub> is able to bind pectin, a polysaccharide ubiquitous in plant material. Mutations that interrupt the closed conformation increase the affinity of the protein to pectin, suggesting that the flap contributes mechanistically to pectin binding. Furthermore, in vivo, the pilus contributes to gastrointestinal (GI) tract colonization in the absence of the type 1 pilus. Hence, we report the ability of YehD to bind pectin representing a possible colonization mechanism of the GI tract via a structurally distinct CUP adhesin.

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Publication Details

Journal
Science Advances
Published
2026-01-07
DOI
https://doi.org/10.1126/sciadv.adz1301
Primary Topic
Escherichia coli research studies
Type
article
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article

The Yeh pilus adhesin is equipped with an α-helical flap motif, which contributes to pectin adherence

Maxwell I. Zimmerman, Jesús Bazán Villicaña, Gregory R. Bowman, Kevin O. Tamadonfar et al.
Science Advances
Escherichia coli research studies
article

The Yeh pilus adhesin is equipped with an α-helical flap motif, which contributes to pectin adherence

Maxwell I. Zimmerman, Jesús Bazán Villicaña, Gregory R. Bowman, Kevin O. Tamadonfar, Justin R. Porter, Bo Huey Chiang, Philippe Azimzadeh, Scott J. Hultgren, Michael L. Patnode, Jerome S. Pinkner, Edward D. B. Lopatto, Karen Dodson, Denise A. Sanick, Roger D. Klein, George M. H. Birchenough, Nathaniel C. Gualberto
article en

Abstract

The Yeh chaperone-usher pathway (CUP) pilus adhesin is encoded in one-half of all <i>Escherichia coli</i>. Yet little is known about its structure and function in <i>E. coli</i> persistence and pathogenesis. Structural investigations reveal that the adhesin receptor binding domains (RBDs) of YehD and its relative YhlD both share a canonical β-rich core and an α-helical flap motif that is hinged at the distal end of the core. This flap was observed in both open and closed conformations using molecular dynamics simulations. The closed conformation is dependent on a hydrophobic patch of amino acids on the distal end of the flap. Functionally, YehD<sub>RBD</sub> is able to bind pectin, a polysaccharide ubiquitous in plant material. Mutations that interrupt the closed conformation increase the affinity of the protein to pectin, suggesting that the flap contributes mechanistically to pectin binding. Furthermore, in vivo, the pilus contributes to gastrointestinal (GI) tract colonization in the absence of the type 1 pilus. Hence, we report the ability of YehD to bind pectin representing a possible colonization mechanism of the GI tract via a structurally distinct CUP adhesin.

Science AdvancesVol. 12(2)
University of California, Santa Cruz (US), Washington University in St. Louis (US), Institute for Biomedicine (IT), Wallenberg Wood Science Center (SE), University of Pennsylvania (US), University of Gothenburg (SE)
Life in Land
Openalex Percentile: Top 94%
Escherichia coli research studies
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