Attachmentoftheubiquitinpeptidetoproteinstargetsthemforproteolyticdegradationbyacomplexcellularstructure,theproteasome.Theregulatedproteolysisofproteinsbyproteasomesremovesdenatured,damagedorimproperlytranslatedproteinsfromcellsandregulatesthelevelofproteinslikecyclinsorsometranscriptionfactors.E1andE2enzymesprepareubiquitinchainsthatarethenattachedtoproteinsbytheE3enzyme.Thesequenceofubiquitinandthebasicstructureandfunctionoftheproteasomearehighlyconserved.Thecoreproteasomeinman(20Sproteasome)consistsoffourringseachwith14subunitsstackedontopofeachotherthatareresponsIBLefortheproteolyticactivityoftheproteasome.ThePA700regulatorycomplexisstackedontheendsofthecylindricalcoretoforma26Sproteasome.Proteinsthataretaggedwithubiquitinarerecognizedandboundbytheregulatorysubunits,thenunfoldedinanATP-dependentmanner,andinsertedintothecoreparticle,whereproteasesdegradetheprotein,releasingsmallpeptidesandreleasingtheubiquitinintact.ThePA28regulatorycomplexisalternativeregulatorycomplexthatappearstoplayaroleinantigenprocessingforpresentationofpeptidestoimmunecellsintheMHCIcomplex.

Contributor:GlennCroston,PhD

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