Cytochrome oxidase is a large multiprotein complex located in the inner mitochondrial membrane, where it functions as the terminal enzyme in the electron-transport chain (discussed in Chapter 14). (A) The first 18 amino acids of the precursor to subunit IV of this enzyme serve as a signal sequence for import of the subunit into the mitochondrion. (B) When the signal sequence is folded as an α helix, the positively charged residues (red) are seen to be clustered on one face of the helix, while the nonpolar residues (yellow) are clustered primarily on the opposite face. Mitochondrial matrix-targeting sequences always have the potential to form such an amphipathic α helix, which is recognized by specific receptor proteins on the mitochondrial surface.