Journal article
Crystal structure of the MrkD(1P) receptor binding domain of Klebsiella pneumoniae and identification of the human collagen V binding interface
Molecular microbiology, Vol.86(4), pp.882-893
11/01/2012
DOI: 10.1111/mmi.12023
PMID: 22988966
Abstract
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 MrkD(1P) receptor domain (MrkDrd). The structure reveals a jelly-roll beta-barrel fold comprising 17 beta-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 MrkD(1P) 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 beta 2a, beta 9b and beta 6 including residues V49, T52, V91, R102 and I136. Taken together, these data provide structural and functional insights on MrkD(1P) recognition of host cells, providing a tool for future development of rationally designed drugs with the prospect of blocking Klebsiella adhesion to collagen V.
Details
- Title: Subtitle
- Crystal structure of the MrkD(1P) receptor binding domain of Klebsiella pneumoniae and identification of the human collagen V binding interface
- Creators
- Ana Toste Rego - University College LondonJeremiah G. Johnson - University of IowaSebastian Geibel - University College LondonFrancisco J. Enguita - University of LisbonSteven Clegg - University of IowaGabriel Waksman - Birkbeck, University of London
- Resource Type
- Journal article
- Publication Details
- Molecular microbiology, Vol.86(4), pp.882-893
- Publisher
- Wiley
- DOI
- 10.1111/mmi.12023
- PMID
- 22988966
- ISSN
- 0950-382X
- eISSN
- 1365-2958
- Number of pages
- 12
- Grant note
- SFRH/BD/22254/2005 / Fundacao para a Ciencia e Tecnologia; Fundacao para a Ciencia e a Tecnologia (FCT) SFRH/BD/22254/2005 / Fundao para a Cincia e a Tecnologia T32 AI007511 / NIH training Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA AI1050011 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 85602 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0800002 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0800002 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
- Language
- English
- Date published
- 11/01/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696566402771
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