Functional attributes of hemoglobin-heme uptake receptors: HmbR of Neisseria meningitidis and HemR of Yersinia enterocolitica

The scavenging approach to iron assimilation employed by bacteria in nature, secretion and receptor-mediated uptake of siderophores (small iron chelating molecules) is frustrated in vivo by host proteins which sequester iron. Numerous pathogens respond with piracy, expressing receptors specific for host proteins which bind or contain iron. This study focuses on two receptors, HmbR of Neisseria meningitidis and HemR of Yersinia enterocolitica, which allow bacteria to pirate heme from hemoglobin (Hb), the most abundant reservoir of iron in the human body. These receptors are members of the heme-uptake subfamily of a large group of TonB-dependent outer membrane receptors through which gram-negative bacteria assimilate iron. The mechanics by which heme is extracted or by which heme or siderophores are transported by any of these receptors are not yet understood. This study used genetic and biochemical approaches to isolate discrete functionalities in HmbR and HemR and to identify functionally important residues and domains within the receptor molecules. Hb binding and heme transport were observed to be separate functions in both receptors. In HmbR, peptide scanning and affinity chromatography identified several regions important for Hb binding, and a deletion mutation implicates the N-terminal region in transport regulation. In HemR, site-directed mutations implicate specific histidine residues in heme transport. Results of this study suggest that HmbR and HemR might represent divergent responses to the task of heme assimilation.