Editing Prion (section)

==== PrP<sup>C</sup> ====
PrP<sup>C</sup> is a normal protein found on the [[cell membrane|membranes]] of [[cell (biology)|cells]], "including several blood components of which [[platelets]] constitute the largest reservoir in humans."<ref name="robertson06">{{cite journal | vauthors = Robertson C, Booth SA, Beniac DR, Coulthart MB, Booth TF, McNicol A | title = Cellular prion protein is released on exosomes from activated platelets | journal = Blood | volume = 107 | issue = 10 | pages = 3907–11 | date = May 2006 | pmid = 16434486 | doi = 10.1182/blood-2005-02-0802 | s2cid = 34141310 | doi-access = free }}</ref> It has 209 [[amino acid]]s (in humans), one [[disulfide bond]], a molecular mass of 35–36 [[Atomic mass unit|kDa]] and a mainly [[alpha helix|alpha-helical]] structure.<ref>{{cite journal | vauthors = Riek R, Hornemann S, Wider G, Glockshuber R, Wüthrich K | title = NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231) | journal = FEBS Letters | volume = 413 | issue = 2 | pages = 282–8 | date = August 1997 | pmid = 9280298 | doi = 10.1016/S0014-5793(97)00920-4 | s2cid = 39791520 | bibcode = 1997FEBSL.413..282R | url = https://www.zora.uzh.ch/id/eprint/191727/1/S0014-5793%2897%2900920-4.pdf }}</ref><ref>{{cite journal | vauthors = Donne DG, Viles JH, Groth D, Mehlhorn I, James TL, Cohen FE, Prusiner SB, Wright PE, Dyson HJ | title = Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 25 | pages = 13452–7 | date = December 1997 | pmid = 9391046 | pmc = 28326 | doi = 10.1073/pnas.94.25.13452 | doi-access = free | bibcode = 1997PNAS...9413452D }}</ref> Several [[Protein topology|topological]] forms exist; one cell surface form anchored via [[glycolipid]] and two [[transmembrane]] forms.<ref>{{cite journal | vauthors = Hegde RS, Mastrianni JA, Scott MR, DeFea KA, Tremblay P, Torchia M, DeArmond SJ, Prusiner SB, Lingappa VR | title = A transmembrane form of the prion protein in neurodegenerative disease | journal = Science | volume = 279 | issue = 5352 | pages = 827–834 | date = February 1998 | pmid = 9452375 | doi = 10.1126/science.279.5352.827 | url = http://pdfs.semanticscholar.org/4320/9efc152784dbc7f0b9a1300d0ec9be602a2c.pdf | url-status = dead | s2cid = 20176119 | bibcode = 1998Sci...279..827H | archive-url = https://web.archive.org/web/20190223062543/http://pdfs.semanticscholar.org/4320/9efc152784dbc7f0b9a1300d0ec9be602a2c.pdf | archive-date = 2019-02-23 }}</ref> The normal protein is not sedimentable; meaning that it cannot be separated by [[Laboratory centrifuge|centrifuging techniques]].<ref name=Krull>{{cite book | vauthors = Carp RI, Kascap RJ | chapter = Taking aim at the transmissible spongiform encephalopathie's infectious agents | veditors = Krull IS, Nunnally BK | title = Prions and mad cow disease | publisher = Marcel Dekker | location = New York | year = 2004 | page = 6 | isbn = 978-0-8247-4083-2 | chapter-url = https://books.google.com/books?id=WjeuaHopV5UC&pg=PA6 | access-date = 2020-06-02 | archive-date = 2020-08-20 | archive-url = https://web.archive.org/web/20200820011006/https://books.google.com/books?id=WjeuaHopV5UC&pg=PA6 | url-status = live }}</ref> It has a complex [[Protein function|function]], which continues to be investigated. PrP<sup>C</sup> [[Chemical bond|binds]] [[copper]](II) [[ion]]s (those in a +2 [[oxidation state]]) with [[high affinity]].<ref>{{cite journal | vauthors = Brown DR, Qin K, Herms JW, Madlung A, Manson J, Strome R, Fraser PE, Kruck T, von Bohlen A, Schulz-Schaeffer W, Giese A, Westaway D, Kretzschmar H | title = The cellular prion protein binds copper in vivo | journal = Nature | volume = 390 | issue = 6661 | pages = 684–7 | year = 1997 | pmid = 9414160 | doi = 10.1038/37783 | s2cid = 4388803 | bibcode = 1997Natur.390..684B }}</ref> This property is supposed to play a role in PrP<sup>C</sup>’s [[anti-oxidative]] properties via reversible [[oxidation]] of the [[Protein structure|N-terminal’s]] [[methionine]] residues into [[sulfoxide]].<ref>{{cite journal |last1=Arcos-López |first1=Trinidad |title=Spectroscopic and Theoretical Study of CuI Binding to His111 in the Human Prion Protein Fragment 106–115 |journal=Organic Chemistry 2016 |date=1 March 2016 |volume=55 |issue=Inorganic Chemistry 2016 |pages=2909–22 |doi=10.1021/acs.inorgchem.5b02794 |pmid=26930130 |pmc=4804749 |hdl=11336/52826 |hdl-access=free }}</ref> Moreover, studies have suggested that, [[in vivo]], due to PrP<sup>C</sup>’s low [[Binding selectivity|selectivity]] to metallic substrates, the protein’s anti oxidative function is impaired when in contact with metals other than [[copper]].<ref>{{cite journal |last1=Wong |first1=Boon-Seng |title=A Yin-Yang role for metals in prion disease |journal=Panminerva Medica (2001) |date=December 2001 |volume=43 |issue=4 |pages=283–7 |pmid=11677424 |url=https://pubmed.ncbi.nlm.nih.gov/11677424/ |access-date=12 November 2024}}</ref> PrP<sup>C</sup> is readily [[Digestion|digested]] by [[proteinase K]] and can be [[Exocytosis|liberated]] from the cell surface by the enzyme [[phospholipase C|phosphoinositide phospholipase C]] (PI-PLC), which [[Bond cleavage|cleaves]] the [[glycophosphatidylinositol]] (GPI) glycolipid anchor.<ref name="weissmann">{{cite journal | vauthors = Weissmann C | title = The state of the prion | journal = Nature Reviews. Microbiology | volume = 2 | issue = 11 | pages = 861–871 | date = November 2004 | pmid = 15494743 | doi = 10.1038/nrmicro1025 | s2cid = 20992257 }}</ref> PrP plays an important role in [[cell-cell adhesion]] and [[intracellular signaling]] ''in vivo'',<ref>{{cite journal | vauthors = Málaga-Trillo E, Solis GP, Schrock Y, Geiss C, Luncz L, Thomanetz V, Stuermer CA | title = Regulation of embryonic cell adhesion by the prion protein | journal = PLOS Biology | volume = 7 | issue = 3 | pages = e55 | date = March 2009 | pmid = 19278297 | pmc = 2653553 | doi = 10.1371/journal.pbio.1000055 | veditors = Weissmann C | doi-access = free }}</ref> and may therefore be involved in cell-cell communication in the brain.<ref>{{Cite journal | vauthors =  Liebert A, Bicknell B, Adams R |date=2014 |title=Prion Protein Signaling in the Nervous System—A Review and Perspective |journal=Signal Transduction Insights |language=en |volume=3 |pages=STI.S12319 |doi=10.4137/STI.S12319 |issn=1178-6434|doi-access=free }}</ref>