Editing ATP synthase (section)

== Structure and function ==
[[File:Fo subunit of ATPase C1. Picture Created in PyMol.png|thumb|289x289px|Bovine mitochondrial ATP synthase. The F<sub>O</sub>, F<sub>1</sub>, axle, and stator regions are color coded magenta, green, orange, and cyan respectively i.e. <span style="color:#f0f">F<sub>O</sub></span>, <span style="color:#0f0">F<sub>1</sub></span>, <span style="color:#f80">axle</span>, <span style="color:#0ff">stator</span>.<ref name="pmid26439008">{{PDB|5ARA}}; {{cite journal | vauthors = Zhou A, Rohou A, Schep DG, Bason JV, Montgomery MG, Walker JE, Grigorieff N, Rubinstein JL | display-authors = 6 | title = Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM | journal = eLife | volume = 4 | pages = e10180 | date = October 2015 | pmid = 26439008 | pmc = 4718723 | doi = 10.7554/eLife.10180 | doi-access = free }}</ref><ref>{{cite journal | doi = 10.2210/rcsb_pdb/mom_2005_12 | journal = Molecule of the Month | title = ATP Synthase | url = https://pdb101.rcsb.org/motm/72 | first = David | last = Goodsell | name-list-style = vanc | date = December 2005 | url-access = subscription }}</ref>]]
[[File:Atpsynthase.jpg|thumb|150px|Simplified model of F<sub>O</sub>F<sub>1</sub>-ATPase alias ATP synthase of ''E. coli''. Subunits of the enzyme are labeled accordingly.]]
[[File:Atpsyntase4.jpg|thumb|150px|Rotation engine of ATP synthase.]]

Located within the [[thylakoid membrane]] and the [[inner mitochondrial membrane]], ATP synthase consists of two regions F<sub>O</sub> and F<sub>1</sub>. F<sub>O</sub> causes rotation of F<sub>1</sub> and is made of c-ring and subunits a, two b, F6. F<sub>1</sub> is made of α, β, γ, and δ subunits. F<sub>1</sub> has a water-soluble part that can hydrolyze ATP. F<sub>O</sub> on the other hand has mainly hydrophobic regions. F<sub>O</sub> F<sub>1</sub> creates a pathway for protons movement across the membrane.<ref name="Velours_2000">{{cite journal | vauthors = Velours J, Paumard P, Soubannier V, Spannagel C, Vaillier J, Arselin G, Graves PV | title = Organisation of the yeast ATP synthase F(0):a study based on cysteine mutants, thiol modification and cross-linking reagents | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1458 | issue = 2–3 | pages = 443–456 | date = May 2000 | pmid = 10838057 | doi = 10.1016/S0005-2728(00)00093-1 | doi-access = free }}</ref>

=== F<sub>1</sub> region ===
The F<sub>1</sub> portion of ATP synthase is [[hydrophilic]] and responsible for hydrolyzing ATP. The F<sub>1</sub> unit protrudes into the [[mitochondrial matrix]] space. Subunits α and β make a hexamer with 6 binding sites. Three of them are catalytically inactive and they bind ADP.

Three other subunits catalyze the ATP synthesis. The other F<sub>1</sub> subunits γ, δ, and ε are a part of a rotational motor mechanism (rotor/axle). The γ subunit allows β to go through conformational changes (i.e., closed, half open, and open states) that allow for ATP to be bound and released once synthesized. The F<sub>1</sub> particle is large and can be seen in the transmission electron microscope by negative staining.<ref>{{cite journal | vauthors = Fernandez Moran H, Oda T, Blair PV, Green DE | title = A macromolecular repeating unit of mitochondrial structure and function. Correlated electron microscopic and biochemical studies of isolated mitochondria and submitochondrial particles of beef heart muscle | journal = The Journal of Cell Biology | volume = 22 | issue = 1 | pages = 63–100 | date = July 1964 | pmid = 14195622 | pmc = 2106494 | doi = 10.1083/jcb.22.1.63 }}</ref> These are particles of 9&nbsp;nm diameter that pepper the inner mitochondrial membrane.

{| class="wikitable" style="text-align:center"
|+ F<sub>1</sub> – Subunits<ref name=pmid24878343/>

|-
! Subunit !! Human Gene !! Note
|-
| [[ATP synthase alpha/beta subunits|alpha]] || ''[[ATP5A1]]'', ''[[ATPAF2]]'' ||
|-
| [[ATP synthase alpha/beta subunits|beta]] || ''[[ATP5B]]'', ''[[ATPAF1]]'' ||
|-
| [[ATP synthase gamma subunit|gamma]] || ''[[ATP5C1]]'' ||
|-
| [[ATP synthase delta/epsilon subunit|delta]] || ''[[ATP5D]]'' || Mitochondrial "delta" is bacterial/chloroplastic epsilon.
|-
| [[ATP synthase epsilon subunit, mitochondrial|epsilon]] || ''[[ATP5E]]'' || Unique to mitochondria.
|-
| [[ATP synthase delta/OSCP subunit|OSCP]] || ''[[ATP5O]]'' || Called "delta" in bacterial and chloroplastic versions.
|}

=== F<sub>O</sub> region ===
[[File:Fo complex subunit F6.png|thumb|285x285px|F<sub>O</sub> subunit F6 from the peripheral stalk region of ATP synthase.<ref name="Carbajo_2004">{{PDB|1VZS}}; {{cite journal | vauthors = Carbajo RJ, Silvester JA, Runswick MJ, Walker JE, Neuhaus D | title = Solution structure of subunit F(6) from the peripheral stalk region of ATP synthase from bovine heart mitochondria | journal = Journal of Molecular Biology | volume = 342 | issue = 2 | pages = 593–603 | date = September 2004 | pmid = 15327958 | doi = 10.1016/j.jmb.2004.07.013 }}</ref>]]

F<sub>O</sub> is a water [[insoluble]] protein with eight subunits and a transmembrane ring. The ring has a [[tetramer]]ic shape with a [[helix-loop-helix]] protein that goes through conformational changes when protonated and deprotonated, pushing neighboring subunits to rotate, causing the spinning of F<sub>O</sub> which then also affects conformation of F<sub>1</sub>, resulting in switching of states of alpha and beta subunits. The F<sub>O</sub> region of ATP synthase is a proton pore that is embedded in the mitochondrial membrane. It consists of three main subunits, a, b, and c. Six c subunits make up the rotor ring, and subunit b makes up a stalk connecting to F<sub>1</sub> OSCP that prevents the αβ hexamer from rotating. Subunit a connects b to the c ring.<ref name=ecoli/> Humans have six additional subunits, [[ATP5H|d]], [[ATP5I|e]], [[ATP5J2|f]], [[ATP5L|g]], [[ATP5J|F6]], and [[MT-ATP8|8]] (or A6L). This part of the enzyme is located in the mitochondrial inner membrane and couples proton translocation to the rotation that causes ATP synthesis in the F<sub>1</sub> region.

In eukaryotes, mitochondrial F<sub>O</sub> forms membrane-bending dimers. These dimers self-arrange into long rows at the end of the [[cristae]], possibly the first step of cristae formation.<ref>{{cite journal | vauthors = Blum TB, Hahn A, Meier T, Davies KM, Kühlbrandt W | title = Dimers of mitochondrial ATP synthase induce membrane curvature and self-assemble into rows | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 10 | pages = 4250–4255 | date = March 2019 | pmid = 30760595 | pmc = 6410833 | doi = 10.1073/pnas.1816556116 | bibcode = 2019PNAS..116.4250B | doi-access = free }}</ref> An atomic model for the dimeric yeast F<sub>O</sub> region was determined by cryo-EM at an overall resolution of 3.6 Å.<ref>{{cite journal | vauthors = Guo H, Bueler SA, Rubinstein JL | title = Atomic model for the dimeric F<sub>O</sub> region of mitochondrial ATP synthase | journal = Science | volume = 358 | issue = 6365 | pages = 936–940 | date = November 2017 | pmid = 29074581 | pmc = 6402782 | doi = 10.1126/science.aao4815 | bibcode = 2017Sci...358..936G }}</ref>
{| class="wikitable" style="text-align:center"
|+ F<sub>O</sub>-Main subunits
|-
! Subunit !! Human Gene
|-
| a || ''[[MT-ATP6]]''
|-
| b || ''[[ATP5PB]]''
|-
| [[ATP synthase subunit C|c]] || ''[[ATP5MC1]]'', ''[[ATP5G2]]'', ''[[ATP5G3]]''
|-
|}