| Structural highlights
Function
[ATIF1_BOVIN] Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
The structure of bovine IF(1), the regulatory subunit of mitochondrial F-ATPase.,Cabezon E, Runswick MJ, Leslie AG, Walker JE EMBO J. 2001 Dec 17;20(24):6990-6. PMID:11742976[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Klein G, Satre M, Dianoux AC, Vignais PV. Radiolabeling of natural adenosine triphosphatase inhibitor with phenyl (14C)isothiocyanate and study of its interaction with mitochondrial adenosine triphosphatase. Localization of inhibitor binding sites and stoichiometry of binding. Biochemistry. 1980 Jun 24;19(13):2919-25. PMID:7397110
- ↑ Cabezon E, Butler PJ, Runswick MJ, Walker JE. Modulation of the oligomerization state of the bovine F1-ATPase inhibitor protein, IF1, by pH. J Biol Chem. 2000 Aug 18;275(33):25460-4. PMID:10831597 doi:10.1074/jbc.M003859200
- ↑ Ando C, Ichikawa N. Glutamic acid in the inhibitory site of mitochondrial ATPase inhibitor, IF(1), participates in pH sensing in both mammals and yeast. J Biochem. 2008 Oct;144(4):547-53. doi: 10.1093/jb/mvn100. Epub 2008 Aug 7. PMID:18687699 doi:http://dx.doi.org/10.1093/jb/mvn100
- ↑ Bason JV, Runswick MJ, Fearnley IM, Walker JE. Binding of the inhibitor protein IF(1) to bovine F(1)-ATPase. J Mol Biol. 2011 Feb 25;406(3):443-53. doi: 10.1016/j.jmb.2010.12.025. Epub 2010 , Dec 28. PMID:21192948 doi:http://dx.doi.org/10.1016/j.jmb.2010.12.025
- ↑ Cabezon E, Montgomery MG, Leslie AG, Walker JE. The structure of bovine F1-ATPase in complex with its regulatory protein IF1. Nat Struct Biol. 2003 Sep;10(9):744-50. Epub 2003 Aug 17. PMID:12923572 doi:http://dx.doi.org/10.1038/nsb966
- ↑ Gledhill JR, Montgomery MG, Leslie AG, Walker JE. How the regulatory protein, IF(1), inhibits F(1)-ATPase from bovine mitochondria. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15671-6. Epub 2007 Sep 25. PMID:17895376
- ↑ Cabezon E, Runswick MJ, Leslie AG, Walker JE. The structure of bovine IF(1), the regulatory subunit of mitochondrial F-ATPase. EMBO J. 2001 Dec 17;20(24):6990-6. PMID:11742976 doi:10.1093/emboj/20.24.6990
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