An induced fit conformational change underlies the binding mechanism of the heme transport proteobacteria-protein HemS.
Bacteria rely on their environment and/or host to acquire iron and have evolved specialized systems to sequester and transport heme. The heme uptake system HemRSTUV is common to proteobacteria, and a major challenge is to understand the molecular mechanism of heme binding and transfer between the protein molecules that underlie this heme transport relay process. In the Gram-negative pathogen Yersinia enterocolitica, the HemRSTUV system culminates with the cytoplasmic recipient HemS, which stores and delivers heme for cellular needs. HemS belongs to a family of proteins essential and unique to proteobacteria. Here we report on the binding mechanism of HemS based on structural data from its apo- and ligand-loaded forms. This heme carrier protein associates with its cargo through a novel, partly preformed binding pocket, formed between a large beta-sheet dome and a three-helix subdomain. In addition to a histidine interacting with the iron, the complex is stabilized by a distal non-coordinating arginine that packs along the porphyrin plane and extensive electrostatic contacts that firmly anchor the heme propionate groups within the protein. Comparison of apo- and ligand-bound HemS crystal structures reveals striking conformational changes that underlie a "heme-induced fit" binding mechanism. Local shifts in amino acid positions combine with global, rigid body-like domain movements, and together, these bring about a switch from an open, apo-form to a closed, bound state. This is the first report in which both liganded and unliganded forms of a heme transport protein are described, thus providing penetrating insights into its mechanism of heme binding and release.
Schneider
Sabine
S
School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD.
Sharp
Katherine H
KH
Barker
Paul D
PD
Paoli
Max
M
D001692:Biological Transport; D006420:Hemeproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D020560:Proteobacteria / Q000737:chemistry*; D055672:Static Electricity
D006420:Hemeproteins; D006639:Histidine