Crystal structure of the MrkD1P receptor binding domain of Klebsiella pneumoniae and identification of the human collagen V binding interface

Authors

  • Ana Toste Rêgo,

    1. Institute of Structural and Molecular Biology, University College London and Birkbeck College, London, UK
    Current affiliation:
    1. MRC Laboratory of Molecular Biology, Cambridge, UK
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  • Jeremiah G. Johnson,

    1. Department of Microbiology, College of Medicine, University of Iowa, Iowa City, Iowa, USA
    Current affiliation:
    1. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
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  • Sebastian Geibel,

    1. Institute of Structural and Molecular Biology, University College London and Birkbeck College, London, UK
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  • Francisco J. Enguita,

    1. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
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  • Steven Clegg,

    1. Department of Microbiology, College of Medicine, University of Iowa, Iowa City, Iowa, USA
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  • Gabriel Waksman

    Corresponding author
    1. Institute of Structural and Molecular Biology, University College London and Birkbeck College, London, UK
    2. Research Department of Structural and Molecular Biology, University College London, UK
    • Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
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For correspondence. E-mail g.waksman@bbk.ac.uk or g.waksman@ucl.ac.uk; Tel. (+44) 020 7631 6833; Fax (+44) 020 7631 6803.

Summary

Klebsiella species are members of the family enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. Among other virulence factors in Klebsiella, type 3 pili exhibit a unique binding pattern in the human kidney via interaction of two MrkD adhesion variants 1C1 and 1P to type IV and/or V collagen. However, very little is known about the nature of this recognition. Here we present the crystal structure of the plasmid born MrkD1P receptor domain (MrkDrd). The structure reveals a jelly-roll β-barrel fold comprising 17 β-strands very similar to the receptor domain of GafD, the tip adhesin from the F17 pilus that recognizes n-acetyl-d-glucosamine (GlcNAc). Analysis of collagen V binding of different MrkD1P mutants revealed that two regions were responsible for its binding: a pocket, that aligns approximately with the GlcNAc binding pocket of GafD involving residues R105 and Y155, and a transversally oriented patch that spans strands β2a, β9b and β6 including residues V49, T52, V91, R102 and I136. Taken together, these data provide structural and functional insights on MrkD1P recognition of host cells, providing a tool for future development of rationally designed drugs with the prospect of blocking Klebsiella adhesion to collagen V.

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