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Publication Abstract from PubMed

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 beta2a, beta9b and beta6 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.

Crystal structure of the MrkD(1P) receptor binding domain of Klebsiella pneumoniae and identification of the human collagen V binding interface.,Rego AT, Johnson JG, Geibel S, Enguita FJ, Clegg S, Waksman G Mol Microbiol. 2012 Sep 18. doi: 10.1111/mmi.12023. PMID:22988966^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.