Editing Proinsulin (section)

== Structure ==
Proinsulin is made up of 86 [[Residue (amino acid)|residues]] in humans (81 in cows),<ref>{{UniProt Full|P01308| INS_HUMAN}}</ref> and formed by three distinct chains.<ref name="Nolan_1971">{{cite journal | vauthors = Nolan C, Margoliash E, Peterson JD, Steiner DF | title = The structure of bovine proinsulin | journal = The Journal of Biological Chemistry | volume = 246 | issue = 9 | pages = 2780–95 | date = May 1971 | doi = 10.1016/S0021-9258(18)62252-5 | pmid = 4928892 | url = http://www.jbc.org/content/246/9/2780 | doi-access = free }}</ref> The A chain, B chain, and the area connecting the two named the [[C-peptide|C peptide]].<ref name="Nolan_1971" /> The correct structure of proinsulin is crucial for the correct folding of mature insulin, as the placement of the C peptide sets the molecule up to create correctly positioned [[disulfide bonds]] in and between the A and B chains.<ref name="Nolan_1971" /><ref name="Snell_1975">{{cite journal | vauthors = Snell CR, Smyth DG | title = Proinsulin: a proposed three-dimensional structure | journal = The Journal of Biological Chemistry | volume = 250 | issue = 16 | pages = 6291–5 | date = August 1975 | doi = 10.1016/S0021-9258(19)41065-X | pmid = 808541 | url = http://www.jbc.org/content/250/16/6291 | doi-access = free }}</ref> There are three disulfide bonds that are necessary for mature insulin to be the correct structure. Two of these disulfide bonds are between the A and B chains, and one is an intra-A chain bond.<ref name="Nolan_1971" />  The disulfide bonds occur between the seventh residues of the A and B chain, the 20th residue of the A chain and the 19th residue of the B chain, and the 6th and 11th residues of the A chain.<ref name="Weiss_2009">{{cite journal | vauthors = Weiss MA | title = Proinsulin and the genetics of diabetes mellitus | journal = The Journal of Biological Chemistry | volume = 284 | issue = 29 | pages = 19159–63 | date = July 2009 | pmid = 19395706 | pmc = 2740536 | doi = 10.1074/jbc.R109.009936 | doi-access = free }}</ref>

The C peptide is between the A and B chains of proinsulin.<ref name="Nolan_1971" /> The connection between the A chain and C peptide is much more stable than the junction between the C peptide and B chain, with alpha helical features being exhibited near the C peptide-A chain connection.<ref name="Yang_2010">{{cite journal | vauthors = Yang Y, Hua QX, Liu J, Shimizu EH, Choquette MH, Mackin RB, Weiss MA | title = Solution structure of proinsulin: connecting domain flexibility and prohormone processing | journal = The Journal of Biological Chemistry | volume = 285 | issue = 11 | pages = 7847–51 | date = March 2010 | pmid = 20106974 | pmc = 2832934 | doi = 10.1074/jbc.c109.084921 | doi-access = free }}</ref> The C peptide-A chain junction occurs between residues 64 and 65 of proinsulin. These are [[lysine]] and [[arginine]] molecules, respectively.<ref name="Yang_2010" /> The C peptide-B chain connection is between two arginine residues at positions 31 and 32 of proinsulin.<ref name="Yang_2010" />

There is conservation of much of the structure of proinsulin among mammalian species, with much of the residue changes seen from one species to another present in the C peptide.<ref name="Snell_1975" /><ref>{{cite journal | vauthors = Bell GI, Pictet RL, Rutter WJ, Cordell B, Tischer E, Goodman HM | title = Sequence of the human insulin gene | journal = Nature | volume = 284 | issue = 5751 | pages = 26–32 | date = March 1980 | pmid = 6243748 | doi = 10.1038/284026a0 | bibcode = 1980Natur.284...26B | s2cid = 4363706 }}</ref> That said, the residues of the C peptide that are conserved across species interact with similarly conserved residues on the A and B chains.<ref name="Snell_1975" /> Thus, it is hypothesized that these conserved residues are important for the functionality of mature insulin.<ref name="Snell_1975" />
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| [[File:Proinsulin 3.png|frameless|center|upright=1.5|class=skin-invert-image]]
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| 3D Model of proinsulin - A chain is in blue, b chain in red, c peptide in orange. The dibasic cleavage for c peptide and a chain is in green KR (lysine and arginine), the one for c peptide and b chain is in cyan RR (arginine).|3D Model of proinsulin - A chain is in blue, b chain in red, c peptide in orange. The dibasic cleavage for c peptide and a chain is in green KR (lysine and arginine), the one for c peptide and b chain is in cyan RR (arginine).
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