Stanniocalcin 1 binds hemin through a partially conserved heme regulatory motif

Hemin (iron protoporphyrin IX) is a necessary component of many proteins, functioning either as a cofactor or an intracellular messenger. Hemoproteins have diverse functions, such as transportation of gases, gas detection, chemical catalysis and electron transfer. Stanniocalcin 1 (STC1) is a protein involved in respiratory responses of the cell but whose mechanism of action is still undetermined. We examined the ability of STC1 to bind hemin in both its reduced and oxidized states and located Cys114 as the axial ligand of the central iron atom of hemin. The amino acid sequence differs from the established (Cys–Pro) heme regulatory motif (HRM) and therefore presents a novel heme binding motif (Cys–Ser). A STC1 peptide containing the heme binding sequence was able to inhibit both spontaneous and H2O2 induced decay of hemin. Binding of hemin does not affect the mitochondrial localization of STC1.

► Stanniocalcin 1 (STC1) binds heme through novel heme binding motif.
► Central iron atom of heme and cysteine-114 of STC1 are essential for binding.
► STC1 binds Fe2+ and Fe3+ heme.
► STC1 peptide prevents oxidative decay of heme.