Extrinsic conditions influence the self-association and structure of IF 1 , the regulatory protein of mitochondrial ATP synthase
| العنوان: | Extrinsic conditions influence the self-association and structure of IF 1 , the regulatory protein of mitochondrial ATP synthase |
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| المؤلفون: | Basile I. M. Wicky, Jane Clarke, Vytaute Boreikaite, John E. Walker, Ian N. Watt |
| المصدر: | Proceedings of the National Academy of Sciences. 116:10354-10359 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Regulation of gene expression, Enzyme complex, Multidisciplinary, 030102 biochemistry & molecular biology, ATP synthase, biology, Mitochondrion, Inhibitory postsynaptic potential, Antiparallel (biochemistry), 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Monomer, chemistry, ATP hydrolysis, biology.protein, Biophysics |
| الوصف: | The endogenous inhibitor of ATP synthase in mitochondria, called IF1, conserves cellular energy when the proton-motive force collapses by inhibiting ATP hydrolysis. Around neutrality, the 84-amino-acid bovine IF1 is thought to self-assemble into active dimers and, under alkaline conditions, into inactive tetramers and higher oligomers. Dimerization is mediated by formation of an antiparallel α-helical coiled-coil involving residues 44–84. The inhibitory region of each monomer from residues 1–46 is largely α-helical in crystals, but disordered in solution. The formation of the inhibited enzyme complex requires the hydrolysis of two ATP molecules, and in the complex the disordered region from residues 8–13 is extended and is followed by an α-helix from residues 14–18 and a longer α-helix from residue 21, which continues unbroken into the coiled-coil region. From residues 21–46, the long α-helix binds to other α-helices in the C-terminal region of predominantly one of the β-subunits in the most closed of the three catalytic interfaces. The definition of the factors that influence the self-association of IF1 is a key to understanding the regulation of its inhibitory properties. Therefore, we investigated the influence of pH and salt-types on the self-association of bovine IF1 and the folding of its unfolded region. We identified the equilibrium between dimers and tetramers as a potential central factor in the in vivo modulation of the inhibitory activity and suggest that the intrinsically disordered region makes its inhibitory potency exquisitely sensitive and responsive to physiological changes that influence the capability of mitochondria to make ATP. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::7571bfd7d8a7f25e862bcf231332e07e https://doi.org/10.1073/pnas.1903535116 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........7571bfd7d8a7f25e862bcf231332e07e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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