Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF
1
)
Figure 2
IF1: structure and intracellular localization. (a) Schematic representation of bovine IF1. The mature protein is composed of 84 residues and is α-helical along most of its length; an amine-terminal presequence of 25 aminoacids represents the mitochondrial targeting sequence (MTS) required for the trafficking of IF1 into the mitochondrial matrix. In complex, IF1 shows an ordered -terminal region, which adopts a helix-turn-helix structure (HTH: residues 14–50) and is flanked by two disordered regions. The inhibitory domain (ID) is located at the -terminus and is part of the minimal inhibitory sequence (MIS: residues 14–47) necessary for a correct interaction with the domain of the ATP synthase. A calmodulin-binding site (CBS: residues 33–42) have been identified at positions 33–42, followed by a histidine-rich region (HRR: residues 48–70) which is implicated in the pH-sensing mechanism and hence in the dimerization. The dimerization of IF1 depends on the -terminal region, which hosts the dimerization domain (DD: residues 37–84), while the oligomerization domain (OD: residues 32–44) is located in the -terminal region of the protein, so that after oligomerization the inhibitory domain is hidden and the protein inactivated. (b) Immunocytochemical localization of IF1 in HeLa cells: the preferential mitochondrial matrix compartmentalization of the protein is shown by its colocalization with the ATP synthase. Cells were costained with anti-IF1 and anti-F1Fo-ATPsynthase chain antibodies, while DAPI was used for nuclear counterstaining.
