4TSF

The Pathway of Binding of the Intrinsically Disordered Mitochondrial Inhibitor Protein to F1-ATPase

Summary for 4TSF

• Entry DOI: 10.2210/pdb4tsf/pdb
• Related: 2v7q
• Descriptor: ATP synthase subunit alpha, mitochondrial, ATP synthase subunit beta, mitochondrial, ATP synthase subunit gamma, mitochondrial, ... (8 entities in total)
• Functional Keywords: hydrolase
• Biological source: Bos taurus (Bovine); More
• Cellular location: Mitochondrion inner membrane : P19483; Mitochondrion: P00829 P05631 P01096
• Total number of polymer chains: 9
• Total formula weight: 368473.10

Authors

Bason, J.V.,Montgomery, M.G.,Leslie, A.G.W.,Walker, J.E. (deposition date: 2014-06-18, release date: 2014-08-06, Last modification date: 2023-12-20)

Primary citation

Bason, J.V.,Montgomery, M.G.,Leslie, A.G.,Walker, J.E.
Pathway of binding of the intrinsically disordered mitochondrial inhibitor protein to F1-ATPase.
Proc.Natl.Acad.Sci.USA, 111:11305-, 2014

PubMed Abstract: The hydrolysis of ATP by the ATP synthase in mitochondria is inhibited by a protein called IF1. Bovine IF1 has 84 amino acids, and its N-terminal inhibitory region is intrinsically disordered. In a known structure of bovine F1-ATPase inhibited with residues 1-60 of IF1, the inhibitory region from residues 1-50 is mainly α-helical and buried deeply at the α(DP)β(DP)-catalytic interface, where it forms extensive interactions with five of the nine subunits of F1-ATPase but mainly with the β(DP)-subunit. As described here, on the basis of two structures of inhibited complexes formed in the presence of large molar excesses of residues 1-60 of IF1 and of a version of IF1 with the mutation K39A, it appears that the intrinsically disordered inhibitory region interacts first with the αEβE-catalytic interface, the most open of the three catalytic interfaces, where the available interactions with the enzyme allow it to form an α-helix from residues 31-49. Then, in response to the hydrolysis of an ATP molecule and the associated partial closure of the interface to the αTPβTP state, the extent of the folded α-helical region of IF1 increases to residues 23-50 as more interactions with the enzyme become possible. Finally, in response to the hydrolysis of a second ATP molecule and a concomitant 120° rotation of the γ-subunit, the interface closes further to the α(DP)β(DP)-state, allowing more interactions to form between the enzyme and IF1. The structure of IF1 now extends to its maximally folded state found in the previously observed inhibited complex.

PubMed: 25049402
DOI: 10.1073/pnas.1411560111

Experimental method

X-RAY DIFFRACTION (3.2 Å)