Hemopexin: the primary specific carrier of plasma heme

Hemopexin (HPX) is the primary specific carrier of plasma heme and participates in its clearance by transport to the liver. After delivering the heme intracellularly, HPX is released intact into the bloodstream. HPX is formed by two four-bladed beta-propeller domains, resembling two thick disks that lock together at a 90° angle; the face of the N-terminal beta-propeller domain packs against one edge of the C-terminal domain. Each propeller blade comprises a four-stranded antiparallel beta-sheet, with the first and the fourth blades tied together by disulfide bridges. The heme ligand is bound between the two four-bladed beta-propeller domains in a pocket formed by the interdomain linker peptide. Residues His-213 and His-266 coordinate the heme iron atom giving a stable bis-histidyl Fe(III) complex. Heme release results from opening of the heme binding pocket, through movement of the two beta-propeller domains and/or the interdomain linker peptide.