The structure of bovine IF(1), the regulatory subunit of mitochondrial F-ATPase.
In mitochondria, the hydrolytic activity of ATP synthase is regulated by an inhibitor protein, IF(1). Its binding to ATP synthase depends on pH, and below neutrality, IF(1) is dimeric and forms a stable complex with the enzyme. At higher pH values, IF(1) forms tetramers and is inactive. In the 2.2 A structure of the bovine IF(1) described here, the four monomers in the asymmetric unit are arranged as a dimer of dimers. Monomers form dimers via an antiparallel alpha-helical coiled coil in the C-terminal region. Dimers are associated into oligomers and form long fibres in the crystal lattice, via coiled-coil interactions in the N-terminal and inhibitory regions (residues 14-47). Therefore, tetramer formation masks the inhibitory region, preventing IF(1) binding to ATP synthase.
Cabezón
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The Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
Runswick
M J
MJ
Leslie
A G
AG
Walker
J E
JE
D000818:Animals; D002417:Cattle; D019281:Dimerization; D006639:Histidine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*
D006639:Histidine; D006180:Proton-Translocating ATPases