A hinge of the endogeneous ATP synthase inhibitor protein: the link between inhibitory and anchoring domains.
The ATP synthase of bovine heart mitochondria possesses a regulatory subunit called the endogenous inhibitory protein (IF(1)). This subunit regulates the catalytic activity of the F(1) sector in the mitochondrial inner membrane. When DeltamuH(+) falls, IF(1) binds to the enzyme and inhibits ATP hydrolysis. On the other hand, the establishment of a DeltamuH(+) induces the release of the inhibitory action of IF(1), allowing ATP synthesis to proceed. IF(1) is also involved in the dimerization of soluble F(1). Dynamic domain analysis and normal mode analysis of the reported crystallographic structure of IF(1) revealed that it has an effective hinge formed by residues 46-52. Molecular dynamics data of a 27 residue fragment confirmed the existence of the hinge. The hinge may act as a regulatory region that links the inhibitory and anchoring domains of IF(1). The residues assigned to the hinge are conserved between mammals, but not in other species, such as yeasts. Likewise, unlike the heart inhibitor, the yeast protein does not have the residues that allow it to form stable dimers through coiled-coil interactions. Collectively, the data suggest that the hinge and the dimerization domain of the inhibitor protein from bovine heart are related to its ability to form stable dimers and to interact with other subunits of the ATP synthase.
Domínguez-Ramírez
L
L
Departamento de Genética Molecular, Instituto de Fisiología Celular, UNAM, México D.F., Mexico. jdoming@ifc.unam.mx
Gómez-Puyou
A
A
de Gómez-Puyou
M Tuena
MT
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D030562:Databases, Protein; D019281:Dimerization; D006801:Humans; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D000097795:ATPase Inhibitory Protein
D021122:Protein Subunits; D011506:Proteins; D000097795:ATPase Inhibitory Protein