Functional transitions of F0F1-ATPase mediated by the inhibitory peptide IF1 in yeast coupled submitochondrial particles.
The mechanism of inhibition of yeast F(0)F(1)-ATPase by its naturally occurring protein inhibitor (IF1) was investigated in submitochondrial particles by studying the IF1-mediated ATPase inhibition in the presence and absence of a protonmotive force. In the presence of protonmotive force, IF1 added during net NTP hydrolysis almost completely inhibited NTPase activity. At moderate IF1 concentration, subsequent uncoupler addition unexpectedly caused a burst of NTP hydrolysis. We propose that the protonmotive force induces the conversion of IF1-inhibited F(0)F(1)-ATPase into a new form having a lower affinity for IF1. This form remains inactive for ATP hydrolysis after IF1 release. Uncoupling simultaneously releases ATP hydrolysis and converts the latent form of IF1-free F(0)F(1)-ATPase back to the active form. The relationship between the different steps of the catalytic cycle, the mechanism of inhibition by IF1 and the interconversion process is discussed.
Galkin
Mikhail
M
Service de Bioénergétique & CNRS-URA 2096, Gif-sur-Yvette, France.
Venard
Renée
R
Vaillier
Jacques
J
Velours
Jean
J
Haraux
Francis
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology*; D017494:Proton Pumps / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013367:Submitochondrial Particles / Q000201:enzymology*; D014475:Uncoupling Agents / Q000494:pharmacology; D000097795:ATPase Inhibitory Protein
D000255:Adenosine Triphosphate; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D004791:Enzyme Inhibitors; D020558:GTP Phosphohydrolases; D006160:Guanosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases; D011506:Proteins; D017494:Proton Pumps; D014475:Uncoupling Agents; D000097795:ATPase Inhibitory Protein