Editing Cooperative binding (section)

=== Ion channels ===
Most [[ion channel]]s are formed of several identical or pseudo-identical monomers or domains, arranged symmetrically in biological membranes. Several classes of such channels whose opening is regulated by ligands exhibit cooperative binding of these ligands.

It was suggested as early as 1967<ref name=Karlin1967>{{cite journal | vauthors = Karlin A | title = On the application of "a plausible model" of allosteric proteins to the receptor for acetylcholine | journal = Journal of Theoretical Biology | volume = 16 | issue = 2 | pages = 306–20 | date = August 1967 | pmid = 6048545 | doi = 10.1016/0022-5193(67)90011-2 | bibcode = 1967JThBi..16..306K }}</ref> (when the exact nature of those channels was still unknown) that the [[nicotinic receptors|nicotinic acetylcholine receptors]] bound [[acetylcholine]] in a cooperative manner due to the existence of several binding sites. The purification of the receptor<ref name=changeux1970 >{{cite journal | vauthors = Changeux JP, Kasai M, Lee CY | title = Use of a snake venom toxin to characterize the cholinergic receptor protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 67 | issue = 3 | pages = 1241–7 | date = November 1970 | pmid = 5274453 | pmc = 283343 | doi = 10.1073/pnas.67.3.1241 | bibcode = 1970PNAS...67.1241C | doi-access = free }}</ref> and its characterization demonstrated a pentameric structure with binding sites located at the interfaces between subunits, confirmed by the structure of the receptor binding domain.<ref name=Brejc2002>{{cite journal | vauthors = Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK | title = Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors | journal = Nature | volume = 411 | issue = 6835 | pages = 269–76 | date = May 2001 | pmid = 11357122 | doi = 10.1038/35077011 | bibcode = 2001Natur.411..269B | s2cid = 4415937 }}</ref>

[[IP3 receptor|Inositol triphosphate (IP3) receptors]] form another class of ligand-gated ion channels exhibiting cooperative binding.<ref name=Meyer1988>{{cite journal | vauthors = Meyer T, Holowka D, Stryer L | title = Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate | journal = Science | volume = 240 | issue = 4852 | pages = 653–6 | date = April 1988 | pmid = 2452482 | doi = 10.1126/science.2452482 | bibcode = 1988Sci...240..653M }}</ref> The structure of those receptors shows four IP3 binding sites symmetrically arranged.<ref name=Seo2012>{{cite journal | vauthors = Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, Dale P, Li C, Ames JB, Ikura M, Taylor CW | title = Structural and functional conservation of key domains in InsP3 and ryanodine receptors | journal = Nature | volume = 483 | issue = 7387 | pages = 108–12 | date = January 2012 | pmid = 22286060 | pmc = 3378505 | doi = 10.1038/nature10751 | bibcode = 2012Natur.483..108S }}</ref>