title: Crystal structure of hemopexin reveals a novel high-affinity heme site formed between two beta-propeller domains.
abstract: The ubiquitous use of heme in animals poses severe biological and chemical challenges. Free heme is toxic to cells and is a potential source of iron for pathogens. For protection, especially in conditions of trauma, inflammation and hemolysis, and to maintain iron homeostasis, a high-affinity binding protein, hemopexin, is required. Hemopexin binds heme with the highest affinity of any known protein, but releases it into cells via specific receptors. The crystal structure of the heme-hemopexin complex reveals a novel heme binding site, formed between two similar four-bladed beta-propeller domains and bounded by the interdomain linker. The ligand is bound to two histidine residues in a pocket dominated by aromatic and basic groups. Further stabilization is achieved by the association of the two beta-propeller domains, which form an extensive polar interface that includes a cushion of ordered water molecules. We propose mechanisms by which these structural features provide the dual function of heme binding and release.
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Paoli
authors.forename: B F
authors.initials: BF
authors.lastname: Anderson
authors.forename: H M
authors.initials: HM
authors.lastname: Baker
authors.forename: W T
authors.initials: WT
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: E N
authors.initials: EN
authors.lastname: Baker
mesh_terms: D000818:Animals; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006466:Hemopexin / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011817:Rabbits; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D014867:Water; D006418:Heme; D006466:Hemopexin