4Z1M

Bovine F1-ATPase inhibited by three copies of the inhibitor protein IF1 crystallised in the presence of thiophosphate.

Summary for 4Z1M

• Entry DOI: 10.2210/pdb4z1m/pdb
• Related: 1E79 1H8E 2CK3 2JDI 2V7Q 4ASU 4TSF 4tt3
• Descriptor: ATP synthase subunit alpha, mitochondrial, ATP synthase subunit beta, mitochondrial, ATP synthase subunit gamma, mitochondrial, ... (10 entities in total)
• Functional Keywords: hydrolase, inhibitor protein
• Biological source: Bos taurus (Bovine); More
• Cellular location: Mitochondrion inner membrane : P19483; Mitochondrion: P00829 P05631 P01096
• Total number of polymer chains: 10
• Total formula weight: 376764.47

Authors

Bason, J.V.,Montgomery, M.G.,Leslie, A.G.W.,Walker, J.E. (deposition date: 2015-03-27, release date: 2015-05-06, Last modification date: 2024-05-08)

Primary citation

Bason, J.V.,Montgomery, M.G.,Leslie, A.G.,Walker, J.E.
How release of phosphate from mammalian F1-ATPase generates a rotary substep.
Proc.Natl.Acad.Sci.USA, 112:6009-6014, 2015

PubMed Abstract: The rotation of the central stalk of F1-ATPase is driven by energy derived from the sequential binding of an ATP molecule to its three catalytic sites and the release of the products of hydrolysis. In human F1-ATPase, each 360° rotation consists of three 120° steps composed of substeps of about 65°, 25°, and 30°, with intervening ATP binding, phosphate release, and catalytic dwells, respectively. The F1-ATPase inhibitor protein, IF1, halts the rotary cycle at the catalytic dwell. The human and bovine enzymes are essentially identical, and the structure of bovine F1-ATPase inhibited by IF1 represents the catalytic dwell state. Another structure, described here, of bovine F1-ATPase inhibited by an ATP analog and the phosphate analog, thiophosphate, represents the phosphate binding dwell. Thiophosphate is bound to a site in the α(E)β(E)-catalytic interface, whereas in F1-ATPase inhibited with IF1, the equivalent site is changed subtly and the enzyme is incapable of binding thiophosphate. These two structures provide a molecular mechanism of how phosphate release generates a rotary substep as follows. In the active enzyme, phosphate release from the β(E)-subunit is accompanied by a rearrangement of the structure of its binding site that prevents released phosphate from rebinding. The associated extrusion of a loop in the β(E)-subunit disrupts interactions in the α(E)β(E-)catalytic interface and opens it to its fullest extent. Other rearrangements disrupt interactions between the γ-subunit and the C-terminal domain of the α(E)-subunit. To restore most of these interactions, and to make compensatory new ones, the γ-subunit rotates through 25°-30°.

PubMed: 25918412
DOI: 10.1073/pnas.1506465112

Experimental method

X-RAY DIFFRACTION (3.3 Å)