Editing Collagen (section)

==History==
The molecular and packing structures of collagen eluded scientists over decades of research. The first evidence that it possesses a regular structure at the molecular level was presented in the mid-1930s.<ref>{{cite journal | vauthors = Wyckoff RW, Corey RB, Biscoe J | title = X-Ray Reflections of Long Spacing from Tendon | journal = Science | volume = 82 | issue = 2121 | pages = 175–176 | date = August 1935 | pmid = 17810172 | doi = 10.1126/science.82.2121.175 | bibcode = 1935Sci....82..175W }}</ref><ref>{{Cite journal | vauthors = Clark G, Parker E, Schaad J, Warren WJ |title=New measurements of previously unknown large interplanar spacings in natural materials |journal=[[Journal of the American Chemical Society|J. Am. Chem. Soc.]] |year=1935 |volume=57 |issue=8 |page=1509 |doi=10.1021/ja01311a504 }}</ref> Research then concentrated on the conformation of the collagen [[monomer]], producing several competing models, although correctly dealing with the conformation of each individual peptide chain. The triple-helical "Madras" model, proposed by [[G. N. Ramachandran]] in 1955, provided an accurate model of [[quaternary structure]] in collagen.<ref name="Ram1955">{{cite journal | vauthors = Ramachandran GN, Kartha G | title = Structure of collagen | journal = Nature | volume = 176 | issue = 4482 | pages = 593–595 | date = September 1955 | pmid = 13265783 | doi = 10.1038/176593a0 | s2cid = 33745131 | bibcode = 1955Natur.176..593R }}</ref><ref name="Ram1954">{{cite journal | vauthors = Ramachandran GN, Kartha G | title = Structure of collagen | journal = Nature | volume = 174 | issue = 4423 | pages = 269–270 | date = August 1954 | pmid = 13185286 | doi = 10.1038/174269c0 | s2cid = 4284147 | bibcode = 1954Natur.174..269R }}</ref><ref>{{cite journal |journal=Resonance |volume=6 |issue=10 |url=http://www.ias.ac.in/resonance/php/toc.php?vol=06&issue=10 |title=GNR – A Tribute |author=Balasubramanian, D . |pages=2–4 |date=October 2001 |url-status=dead |archive-url=https://web.archive.org/web/20140110164101/http://www.ias.ac.in/resonance/php/toc.php?vol=06&issue=10 |archive-date=10 January 2014 |doi=10.1007/BF02836961 |s2cid=122261106 }}</ref><ref>{{cite journal | vauthors = Leonidas DD, Chavali GB, Jardine AM, Li S, Shapiro R, Acharya KR | title = Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography | journal = Protein Science | volume = 10 | issue = 8 | pages = 1669–1676 | date = August 2001 | pmid = 11468363 | pmc = 2374093 | doi = 10.1110/ps.13601 }}</ref><ref>{{cite journal | vauthors = Subramanian E | title = G.N. Ramachandran | journal = Nature Structural Biology | volume = 8 | issue = 6 | pages = 489–491 | date = June 2001 | pmid = 11373614 | doi = 10.1038/88544 | s2cid = 7231304 | doi-access = free }}</ref> This model was supported by further studies of higher resolution in the late 20th century.<ref>{{cite journal | vauthors = Fraser RD, MacRae TP, Suzuki E | title = Chain conformation in the collagen molecule | journal = Journal of Molecular Biology | volume = 129 | issue = 3 | pages = 463–481 | date = April 1979 | pmid = 458854 | doi = 10.1016/0022-2836(79)90507-2 }}</ref><ref>{{cite journal | vauthors = Okuyama K, Okuyama K, Arnott S, Takayanagi M, Kakudo M | title = Crystal and molecular structure of a collagen-like polypeptide (Pro-Pro-Gly)10 | journal = Journal of Molecular Biology | volume = 152 | issue = 2 | pages = 427–443 | date = October 1981 | pmid = 7328660 | doi = 10.1016/0022-2836(81)90252-7 }}</ref><ref>{{cite journal | vauthors = Traub W, Yonath A, Segal DM | title = On the molecular structure of collagen | journal = Nature | volume = 221 | issue = 5184 | pages = 914–917 | date = March 1969 | pmid = 5765503 | doi = 10.1038/221914a0 | s2cid = 4145093 | bibcode = 1969Natur.221..914T }}</ref><ref>{{cite journal | vauthors = Bella J, Eaton M, Brodsky B, Berman HM | title = Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution | journal = Science | volume = 266 | issue = 5182 | pages = 75–81 | date = October 1994 | pmid = 7695699 | doi = 10.1126/science.7695699 | bibcode = 1994Sci...266...75B }}</ref>

The packing structure of collagen has not been defined to the same degree outside of the fibrillar collagen types, although it has been long known to be hexagonal.<ref name="Hulmes Miller 1979">{{cite journal | vauthors = Hulmes DJ, Miller A | title = Quasi-hexagonal molecular packing in collagen fibrils | journal = Nature | volume = 282 | issue = 5741 | pages = 878–880 | year = 1979 | pmid = 514368 | doi = 10.1038/282878a0 | s2cid = 4332269 | bibcode = 1979Natur.282..878H }}</ref><ref>{{cite journal | vauthors = Jésior JC, Miller A, Berthet-Colominas C | title = Crystalline three-dimensional packing is a general characteristic of type I collagen fibrils | journal = FEBS Letters | volume = 113 | issue = 2 | pages = 238–240 | date = May 1980 | pmid = 7389896 | doi = 10.1016/0014-5793(80)80600-4 | s2cid = 40958154 | doi-access = free | bibcode = 1980FEBSL.113..238J }}</ref><ref>{{Cite journal | vauthors = Fraser RD, MacRae TP |title=Unit cell and molecular connectivity in tendon collagen |journal=[[International Journal of Biological Macromolecules]] |year=1981 |volume=3 |issue=3 |pages=193–200 |doi=10.1016/0141-8130(81)90063-5 }}</ref> As with its monomeric structure, several conflicting models propose either that the packing arrangement of collagen molecules is 'sheet-like', or is [[microfibril]]lar.<ref>{{cite journal | vauthors = Fraser RD, MacRae TP, Miller A | title = Molecular packing in type I collagen fibrils | journal = Journal of Molecular Biology | volume = 193 | issue = 1 | pages = 115–125 | date = January 1987 | pmid = 3586015 | doi = 10.1016/0022-2836(87)90631-0 }}</ref><ref>{{cite journal | vauthors = Wess TJ, Hammersley AP, Wess L, Miller A | title = Molecular packing of type I collagen in tendon | journal = Journal of Molecular Biology | volume = 275 | issue = 2 | pages = 255–267 | date = January 1998 | pmid = 9466908 | doi = 10.1006/jmbi.1997.1449 }}</ref> The microfibrillar structure of collagen fibrils in tendon, cornea and cartilage was imaged directly by [[electron microscopy]] in the late 20th century and early 21st century.<ref>{{cite journal | vauthors = Raspanti M, Ottani V, Ruggeri A | title = Subfibrillar architecture and functional properties of collagen: a comparative study in rat tendons | journal = Journal of Anatomy | volume = 172 | pages = 157–164 | date = October 1990 | pmid = 2272900 | pmc = 1257211 }}</ref><ref>{{cite journal | vauthors = Holmes DF, Gilpin CJ, Baldock C, Ziese U, Koster AJ, Kadler KE | title = Corneal collagen fibril structure in three dimensions: Structural insights into fibril assembly, mechanical properties, and tissue organization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 13 | pages = 7307–7312 | date = June 2001 | pmid = 11390960 | pmc = 34664 | doi = 10.1073/pnas.111150598 | doi-access = free | bibcode = 2001PNAS...98.7307H }}</ref><ref>{{cite journal | vauthors = Holmes DF, Kadler KE | title = The 10+4 microfibril structure of thin cartilage fibrils | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 46 | pages = 17249–17254 | date = November 2006 | pmid = 17088555 | pmc = 1859918 | doi = 10.1073/pnas.0608417103 | doi-access = free | bibcode = 2006PNAS..10317249H }}</ref> The microfibrillar structure of [[rat]] tail tendon was modeled as being closest to the observed structure, although it oversimplified the topological progression of neighboring collagen molecules, and so did not predict the correct conformation of the discontinuous D-periodic pentameric arrangement termed ''microfibril''.<ref name=Orgel>{{cite journal | vauthors = Orgel JP, Irving TC, Miller A, Wess TJ | title = Microfibrillar structure of type I collagen in situ | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 24 | pages = 9001–9005 | date = June 2006 | pmid = 16751282 | pmc = 1473175 | doi = 10.1073/pnas.0502718103 | doi-access = free | bibcode = 2006PNAS..103.9001O }}</ref><ref name=Okuyama>{{cite journal | vauthors = Okuyama K, Bächinger HP, Mizuno K, Boudko S, Engel J, Berisio R, Vitagliano L | title = Re: Microfibrillar structure of type I collagen in situ | journal = Acta Crystallographica. Section D, Biological Crystallography | volume = 65 | issue = Pt 9 | pages = 1009–10 | date = September 2009 | pmid = 19690380 | doi = 10.1107/S0907444909023051 | doi-access = free | bibcode = 2009AcCrD..65.1007O }}</ref><ref>{{cite journal|last1=Orgel|first1=Joseph|title=On the packing structure of collagen: response 0to Okuyama et al.'s comment on Microfibrillar structure of type I collagen in situ|journal=Acta Crystallographica Section D|volume=D65|issue=9|page=1009<!--|pages=1010-->|doi=10.1107/S0907444909028741|year=2009|bibcode=2009AcCrD..65.1009O |doi-access=free}}</ref>