Cabezón E, Runswick M J, Leslie A G, Walker J E
The Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
EMBO J. 2001 Dec 17;20(24):6990-6. doi: 10.1093/emboj/20.24.6990.
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.
在线粒体中,ATP合酶的水解活性受抑制蛋白IF(1)调控。它与ATP合酶的结合取决于pH值,在中性pH以下,IF(1)呈二聚体形式,并与该酶形成稳定复合物。在较高pH值时,IF(1)形成四聚体且无活性。在此处描述的牛IF(1)的2.2埃结构中,不对称单元中的四个单体排列成二聚体的二聚体。单体通过C端区域的反平行α-螺旋卷曲螺旋形成二聚体。二聚体通过N端和抑制区域(第14至47位残基)中的卷曲螺旋相互作用聚合成寡聚体,并在晶格中形成长纤维。因此,四聚体的形成掩盖了抑制区域,阻止IF(1)与ATP合酶结合。