PDBsum entry 4tt3

Hydrolase

PDB id: 4tt3

Contents

Protein chains

487 a.a.

469 a.a.

183 a.a.

40 a.a.

28 a.a.

19 a.a.

Ligands

ATP ×3

GOL ×2

ADP ×2

Metals

_MG ×5

Waters ×28

References listed in PDB file

Key reference

• Title: Pathway of binding of the intrinsically disordered mitochondrial inhibitor protein to f1-Atpase.
• Authors: J.V.Bason, M.G.Montgomery, A.G.Leslie, J.E.Walker.
• Ref.: Proc Natl Acad Sci U S A, 2014, 111, 11305-11310. [DOI no: 10.1073/pnas.1411560111]
• PubMed id: 25049402

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 αDPβDP-catalytic interface, where it forms extensive interactions with five of the nine subunits of F1-ATPase but mainly with the βDP-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 αDPβDP-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.