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

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.