Phosphorylation of the F(1)F(o) ATP synthase beta subunit: functional and structural consequences assessed in a model system.
Phosphorylation of the F(1)F(o) ATP synthase beta subunit: functional and structural consequences assessed in a model system.
复制标题
DOI：
10.1161/circresaha.109.214155
复制
发表时间：
2010-02-19
影响因子：
20.1
通讯作者：
Van Eyk JE
中科院分区：
文献类型：
--
作者：
Kane LA;Youngman MJ;Jensen RE;Van Eyk JE
We previously discovered several phosphorylations to the β subunit of the mitochondrial F1Fo ATP synthase complex in isolated rabbit myocytes upon adenosine treatment, an agent that induces cardioprotection. The role of these phosphorylations is unknown. The current study focuses on the functional consequences of phosphorylation of the ATP synthase complex β subunit by generating non-phosphorylatable and phospho-mimetic analogs in a model system, S. cerevisiae. The four amino acid residues with homology in yeast (T58, S213, T262 and T318) were studied with respect to growth, complex and supercomplex formation, and enzymatic activity (ATPase rate). The most striking mutant was the T262 site, for which the phospho-mimetic (T262E) abolished activity, while the non-phosphorylatable strain (T262A) had an ATPase rate equivalent to wild-type. Although T262E, like all of the β subunit mutants, was able to form the intact complex (F1Fo), this strain lacked a free F1 component found in wild-type and had a corresponding increase of lower molecular weight forms of the protein, indicating an assembly/stability defect. In addition, the ATPase activity was reduced but not abolished with the phospho-mimetic mutation at T58, a site that altered the formation/maintenance of dimers of the F1Fo ATP synthase complex. Taken together, these data show that pseudo-phosphorylation of specific amino acid residues can have separate and distinctive effects on the F1Fo ATP synthase complex, suggesting the possibility that several of the phosphorylations observed in the rabbit heart can have structural and functional consequences to the F1Fo ATP synthase complex.
