Activity and NMR structure of synthetic peptides of the bovine ATPase inhibitor protein, IF1.
The protein IF(1) is a natural inhibitor of the mitochondrial F(o)F(1)-ATPase. Many investigators have been prompted to identify the shortest segment of IF(1), retaining its native activity, for use in biomedical applications. Here, the activity of the synthetic peptides IF(1)-(42-58) and IF(1)-(22-46) is correlated to their structure and conformational plasticity determined by CD and [1H]-NMR spectroscopy. Among all the IF(1) segments tested, IF(1)-(42-58) exerts the most potent, pH and temperature dependent activity on the F(o)F(1) complex. The results suggest that, due to its flexible structure, it can fold in helical and/or beta-spiral arrangements that favor the binding to the F(o)F(1) complex, where the native IF(1) binds. IF(1)-(22-46), instead, as it adopts a rigid alpha-helical conformation, it inhibits ATP hydrolysis only in the soluble F(1) moiety.
de Chiara
Cesira
C
Department of Experimental Medicine, Section of Chemistry and Structural Biochemistry, University of Parma, 43100 Parma, Italy.
Nicastro
Giuseppe
G
Spisni
Alberto
A
Zanotti
Franco
F
Cocco
Tiziana
T
Papa
Sergio
S
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000097795:ATPase Inhibitory Protein
D010455:Peptides; D011506:Proteins; D006180:Proton-Translocating ATPases; D000097795:ATPase Inhibitory Protein