Editing ATP synthase (section)

== Evolution ==
The [[evolution]] of ATP synthase is thought to have been modular whereby two functionally independent subunits became associated and gained new functionality.<ref name=RotaryDNA>{{cite journal | vauthors = Doering C, Ermentrout B, Oster G | title = Rotary DNA motors | journal = Biophysical Journal | volume = 69 | issue = 6 | pages = 2256–2267 | date = December 1995 | pmid = 8599633 | pmc = 1236464 | doi = 10.1016/S0006-3495(95)80096-2 | bibcode = 1995BpJ....69.2256D }}</ref><ref name=LifeScience_IL>{{cite web |first=Antony |last=Crofts |name-list-style=vanc |url=http://www.life.illinois.edu/crofts/bioph354/lect10.html |title=Lecture 10:ATP synthase |publisher=Life Sciences at the [[University of Illinois at Urbana–Champaign]]}}</ref> This association appears to have occurred early in evolutionary history, because essentially the same structure and activity of ATP synthase enzymes are present in all kingdoms of life.<ref name=RotaryDNA /> The F-ATP synthase displays high functional and mechanistic similarity to the [[V-ATPase]].<ref name=InterPro_Synthase>{{cite web |url=http://www.ebi.ac.uk/interpro/potm/2005_12/Page2.htm |work=InterPro Database |title=ATP Synthase }}</ref> However, whereas the F-ATP synthase generates ATP by utilising a proton gradient, the [[V-ATPase]] generates a proton gradient at the expense of ATP, generating pH values of as low as 1.<ref>{{cite journal | vauthors = Beyenbach KW, Wieczorek H | title = The V-type H+ ATPase: molecular structure and function, physiological roles and regulation | journal = The Journal of Experimental Biology | volume = 209 | issue = Pt 4 | pages = 577–589 | date = February 2006 | pmid = 16449553 | doi = 10.1242/jeb.02014 | doi-access = free }}</ref>

<!-- FIXME: Since F1 is now linked to T3SS ring too, this needs a rewrite! -->
The F<sub>1</sub> region also shows significant similarity to hexameric [[DNA helicase]]s (especially the [[Rho factor]]), and the entire enzyme region shows some similarity to {{chem|H|+}}-powered [[T3SS]] or [[Flagellum#Motor|flagellar motor]] complexes.<ref name=InterPro_Synthase /><ref>{{cite journal | vauthors = Skordalakes E, Berger JM | title = Structure of the Rho transcription terminator: mechanism of mRNA recognition and helicase loading | journal = Cell | volume = 114 | issue = 1 | pages = 135–146 | date = July 2003 | pmid = 12859904 | doi = 10.1016/S0092-8674(03)00512-9 | s2cid = 5765103 | doi-access = free }}</ref><ref name=T3SS>{{cite journal | vauthors = Imada K, Minamino T, Uchida Y, Kinoshita M, Namba K | title = Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 13 | pages = 3633–3638 | date = March 2016 | pmid = 26984495 | pmc = 4822572 | doi = 10.1073/pnas.1524025113 | doi-access = free | bibcode = 2016PNAS..113.3633I }}</ref> The α<sub>3</sub>β<sub>3</sub> hexamer of the F<sub>1</sub> region shows significant structural similarity to hexameric DNA helicases; both form a ring with 3-fold rotational symmetry with a central pore. Both have roles dependent on the relative rotation of a macromolecule within the pore; the DNA helicases use the helical shape of DNA to drive their motion along the DNA molecule and to detect supercoiling, whereas the α<sub>3</sub>β<sub>3</sub> hexamer uses the conformational changes through the rotation of the γ subunit to drive an enzymatic reaction.<ref name=EctopicATP>{{cite journal | vauthors = Martinez LO, Jacquet S, Esteve JP, Rolland C, Cabezón E, Champagne E, Pineau T, Georgeaud V, Walker JE, Tercé F, Collet X, Perret B, Barbaras R | display-authors = 6 | title = Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis | journal = Nature | volume = 421 | issue = 6918 | pages = 75–79 | date = January 2003 | pmid = 12511957 | doi = 10.1038/nature01250 | s2cid = 4333137 | bibcode = 2003Natur.421...75M }}</ref>

The {{chem|H|+}} motor of the F<sub>O</sub> particle shows great functional similarity to the {{chem|H|+}} motors that drive flagella.<ref name=InterPro_Synthase /> Both feature a ring of many small alpha-helical proteins that rotate relative to nearby stationary proteins, using a {{chem|H|+}} potential gradient as an energy source. This link is tenuous, however, as the overall structure of flagellar motors is far more complex than that of the F<sub>O</sub> particle and the ring with about 30 rotating proteins is far larger than the 10, 11, or 14 helical proteins in the F<sub>O</sub> complex. More recent structural data do however show that the ring and the stalk are structurally similar to the F<sub>1</sub> particle.<ref name=T3SS/>

[[File:ATP synthesis - ATP synthase rotation.ogv|thumb|right|230px|Conformation changes of ATP synthase during synthesis]]
The modular evolution theory for the origin of ATP synthase suggests that two subunits with independent function, a DNA helicase with ATPase activity and a {{chem|H|+}} motor, were able to bind, and the rotation of the motor drove the ATPase activity of the helicase in reverse.<ref name=RotaryDNA /><ref name=EctopicATP /> This complex then evolved greater efficiency and eventually developed into today's intricate ATP synthases. Alternatively, the DNA helicase/{{chem|H|+}} motor complex may have had {{chem|H|+}} pump activity with the ATPase activity of the helicase driving the {{chem|H|+}} motor in reverse.<ref name=RotaryDNA /> This may have evolved to carry out the reverse reaction and act as an ATP synthase.<ref name=LifeScience_IL /><ref name=Cross1990>{{cite journal | vauthors = Cross RL, Taiz L | title = Gene duplication as a means for altering H+/ATP ratios during the evolution of F<sub>O</sub>F<sub>1</sub> ATPases and synthases | journal = FEBS Letters | volume = 259 | issue = 2 | pages = 227–229 | date = January 1990 | pmid = 2136729 | doi = 10.1016/0014-5793(90)80014-a | s2cid = 32559858 | doi-access = free }}</ref><ref name=Cross2004>{{cite journal | vauthors = Cross RL, Müller V | title = The evolution of A-, F-, and V-type ATP synthases and ATPases: reversals in function and changes in the H+/ATP coupling ratio | journal = FEBS Letters | volume = 576 | issue = 1–2 | pages = 1–4 | date = October 2004 | pmid = 15473999 | doi = 10.1016/j.febslet.2004.08.065 | s2cid = 25800744 | doi-access = free }}</ref>