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Publication Abstract from PubMed

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 degrees rotation consists of three 120 degrees steps composed of substeps of about 65 degrees , 25 degrees , and 30 degrees , 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 alphaEbetaE-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 betaE-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 betaE-subunit disrupts interactions in the alphaEbetaE-catalytic interface and opens it to its fullest extent. Other rearrangements disrupt interactions between the gamma-subunit and the C-terminal domain of the alphaE-subunit. To restore most of these interactions, and to make compensatory new ones, the gamma-subunit rotates through 25 degrees -30 degrees .

How release of phosphate from mammalian F1-ATPase generates a rotary substep.,Bason JV, Montgomery MG, Leslie AG, Walker JE Proc Natl Acad Sci U S A. 2015 Apr 27. pii: 201506465. PMID:25918412^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.