Editing P53 (section)

== Structure ==
[[File:P53 Schematic.tif|thumb|right|A schematic of the known protein domains in p53 (NLS = Nuclear Localization Signal)|360x360px]]
[[File:3KMD p53 DNABindingDomian.png|thumb|Crystal structure of four p53 DNA binding domains (as found in the bioactive homo-tetramer)]]p53 has seven [[domain (protein)|domains]]:
# an acidic [[N-terminus]] transcription-activation domain (TAD), also known as activation domain 1 (AD1), which activates [[transcription factor]]s. The N-terminus contains two complementary transcriptional activation domains, with a major one at residues 1–42 and a minor one at residues 55–75, specifically involved in the regulation of several pro-apoptotic genes.<ref name="pmid9707426">{{cite journal |vauthors=Venot C, Maratrat M, Dureuil C, Conseiller E, Bracco L, Debussche L |date=August 1998 |title=The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific PIG3 gene transactivation and with transcriptional repression |journal=The EMBO Journal |volume=17 |issue=16 |pages=4668–79 |doi=10.1093/emboj/17.16.4668 |pmc=1170796 |pmid=9707426}}</ref>
# activation domain 2 (AD2) important for [[Apoptosis|apoptotic]] activity: residues 43–63.
# [[proline]] rich domain important for the apoptotic activity of p53 by nuclear exportation via [[MAPK]]: residues 64–92.
# central [[DNA]]-binding core domain ([[DNA-binding domain|DBD]]). Contains one zinc atom and several [[arginine]] amino acids: residues 102–292. This region is responsible for binding the p53 co-repressor [[LMO3]].<ref name="Larsen S, Yokochi T, Isogai E, Nakamura Y, Ozaki T, Nakagawara A 2010 252–7">{{cite journal |vauthors=Larsen S, Yokochi T, Isogai E, Nakamura Y, Ozaki T, Nakagawara A |date=February 2010 |title=LMO3 interacts with p53 and inhibits its transcriptional activity |journal=Biochemical and Biophysical Research Communications |volume=392 |issue=3 |pages=252–7 |doi=10.1016/j.bbrc.2009.12.010 |pmid=19995558}}</ref>
# [[Nuclear localization sequence|Nuclear Localization Signaling]] (NLS) domain, residues 316–325.
# homo-oligomerisation domain (OD): residues 307–355. Tetramerization is essential for the activity of p53 ''in vivo''.
# [[C-terminal]] involved in downregulation of DNA binding of the central domain: residues 356–393.<ref name="pmid15713654">{{cite journal |vauthors=Harms KL, Chen X |date=March 2005 |title=The C terminus of p53 family proteins is a cell fate determinant |journal=Molecular and Cellular Biology |volume=25 |issue=5 |pages=2014–30 |doi=10.1128/MCB.25.5.2014-2030.2005 |pmc=549381 |pmid=15713654}}</ref>

Mutations that deactivate p53 in cancer usually occur in the DBD. Most of these mutations destroy the ability of the protein to bind to its target DNA sequences, and thus prevents transcriptional activation of these genes. As such, mutations in the DBD are [[recessive allele|recessive]] [[loss-of-function]] mutations. Molecules of p53 with mutations in the OD dimerise with [[wild-type]] p53, and prevent them from activating transcription. Therefore, OD mutations have a dominant negative effect on the function of p53.

Wild-type p53 is a [[labile]] [[protein]], comprising folded and [[Intrinsically unstructured proteins|unstructured regions]] that function in a synergistic manner.<ref name="pmid12367518">{{cite journal |vauthors=Bell S, Klein C, Müller L, Hansen S, Buchner J |date=October 2002 |title=p53 contains large unstructured regions in its native state |journal=Journal of Molecular Biology |volume=322 |issue=5 |pages=917–27 |doi=10.1016/S0022-2836(02)00848-3 |pmid=12367518}}</ref>

[[SDS-PAGE]] analysis indicates that p53 is a 53-[[kilodalton]] (kDa) protein. However, the actual mass of the full-length p53 protein (p53α) based on the sum of masses of the [[amino acid]] residues is only 43.7&nbsp;kDa. This difference is due to the high number of [[proline]] residues in the protein, which slow its migration on SDS-PAGE, thus making it appear heavier than it actually is.<ref name="pmid7107651">{{cite journal |vauthors=Ziemer MA, Mason A, Carlson DM |date=September 1982 |title=Cell-free translations of proline-rich protein mRNAs |journal=The Journal of Biological Chemistry |volume=257 |issue=18 |pages=11176–80 |doi=10.1016/S0021-9258(18)33948-6 |pmid=7107651 |doi-access=free}}</ref>