Editing Proteasome (section)

==Assembly==
The assembly of the proteasome is a complex process due to the number of subunits that must associate to form an active complex. The β subunits are synthesized with [[N-terminus|N-terminal]] "propeptides" that are [[post-translational modification|post-translationally modified]] during the assembly of the 20S particle to expose the proteolytic active site. The 20S particle is assembled from two half-proteasomes, each of which consists of a seven-membered pro-β ring attached to a seven-membered α ring. The association of the β rings of the two half-proteasomes triggers [[threonine]]-dependent [[Autolysis (biology)|autolysis]] of the propeptides to expose the active site. These β interactions are mediated mainly by [[Salt bridge (protein and supramolecular)|salt bridge]]s and [[hydrophobic]] interactions between conserved [[alpha helix|alpha helices]] whose disruption by [[mutation]] damages the proteasome's ability to assemble.<ref name=Witt>{{cite journal | vauthors = Witt S, Kwon YD, Sharon M, Felderer K, Beuttler M, Robinson CV, Baumeister W, Jap BK | title = Proteasome assembly triggers a switch required for active-site maturation | journal = Structure | volume = 14 | issue = 7 | pages = 1179–88 | date = July 2006 | pmid = 16843899 | doi = 10.1016/j.str.2006.05.019 | doi-access = free }}</ref> The assembly of the half-proteasomes, in turn, is initiated by the assembly of the α subunits into their heptameric ring, forming a template for the association of the corresponding pro-β ring. The assembly of α subunits has not been characterized.<ref name=Kruger>{{cite journal | vauthors = Krüger E, Kloetzel PM, Enenkel C | title = 20S proteasome biogenesis | journal = Biochimie | volume = 83 | issue = 3–4 | pages = 289–93 | year = 2001 | pmid = 11295488 | doi = 10.1016/S0300-9084(01)01241-X }}</ref>

Only recently, the assembly process of the 19S regulatory particle has been elucidated to considerable extent. The 19S regulatory particle assembles as two distinct subcomponents, the base and the lid. Assembly of the base complex is facilitated by four assembly [[chaperone (protein)|chaperone]]s, Hsm3/S5b, Nas2/p27, Rpn14/PAAF1, and Nas6/[[gankyrin]] (names for yeast/mammals).<ref name=Murata>{{cite journal | vauthors = Murata S, Yashiroda H, Tanaka K | title = Molecular mechanisms of proteasome assembly | journal = Nature Reviews Molecular Cell Biology | volume = 10 | issue = 2 | pages = 104–115 | date = February 2009 | pmid = 19165213 | doi = 10.1038/nrm2630 | s2cid = 21263837 }}</ref> These assembly chaperones bind to the AAA-[[ATPase]] subunits and their main function seems to be to ensure proper assembly of the heterohexameric AAA-[[ATPase]] ring. To date it is still under debate whether the base complex assembles separately, whether the assembly is templated by the 20S core particle, or whether alternative assembly pathways exist. In addition to the four assembly chaperones, the deubiquitinating enzyme Ubp6/[[Usp14]] also promotes base assembly, but it is not essential.<ref name=Sakata>{{cite journal | vauthors = Sakata E, Stengel F, Fukunaga K, Zhou M, Saeki Y, Förster F, Baumeister W, Tanaka K, Robinson CV | title = The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory particle | journal = Molecular Cell | volume = 42 | issue = 5 | pages = 637–649 | date = June 2011 | pmid = 21658604 | doi = 10.1016/j.molcel.2011.04.021 | doi-access = free }}</ref> The lid assembles separately in a specific order and does not require assembly chaperones.<ref name=Fukunaga>{{cite journal | vauthors = Fukunaga K, Kudo T, Toh-e A, Tanaka K, Saeki Y | title = Dissection of the assembly pathway of the proteasome lid in Saccharomyces cerevisiae | journal = Biochemical and Biophysical Research Communications | volume = 396 | issue = 4 | pages = 1048–1053 | date = June 2010 | pmid = 20471955 | doi = 10.1016/j.bbrc.2010.05.061 }}</ref>