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

Abstract

Summary: K lebsiella 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 K lebsiella, type 3 pili exhibit a unique binding pattern in the human kidney via interaction of two MrkD adhesion variants 1 C 1 and 1 P 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 β‐barrel fold comprising 17 β‐strands very similar to the receptor domain of GafD, the tip adhesin from the F 17 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 R 105 and Y 155, and a transversally oriented patch that spans strands β2a, β9b and β6 including residues V 49, T 52, V 91, R 102 and I 136. 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 K lebsiella adhesion to collagen V.