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2005-01-18Habilitationsschrift DOI: 10.18452/13957
Strukturelle und funktionelle Zusammenhänge und Unterschiede archaebakterieller und eukaryontischer 20S-Proteasome
dc.contributor.authorGroll, Michael
dc.date.accessioned2017-06-18T00:40:32Z
dc.date.available2017-06-18T00:40:32Z
dc.date.created2005-01-20
dc.date.issued2005-01-18none
dc.identifier.urihttp://edoc.hu-berlin.de/18452/14609
dc.description.abstractIn eukaryotes protein degradation is performed by the ubiquitin-proteasome system. The 26S proteasome, a 2.5MDa large multimeric molecular machine, consists of more than 30 subunits and represents the core component of this proteolytic pathway. The complex is assembled from a proteolytically active 20S proteasome and two 19S regulator cap complexes. So far crystal structure, topology and enzymatic mechanism have only been elucidated for the 20S proteasome core particle (CP). CPs are assembled from four stacked rings of seven subunits each, following an alpha7beta7beta7alpha7-stochiometry. The strict established order of the proteasomal assembly and maturation is essential to prevent uncontrolled and premature protein degradation in the cell. CPs belong to the class of Ntn-hydrolases. Peptide hydrolysis is performed inside a central cavity at the active sites of the beta-type subunits, with Ogam of the hydroxyl group of the N-terminal threonine acting as the nucleophile. Release of the proteolytically active threonine through N-O-Acetyl rearrangement is the last step of the proteasomal assembly. Compartmentalisation of CPs is an important way to regulate substrate access to the central cavity as well as release of the generated oligopeptides. The activity of eukaryotic CPs are controlled by an unique mechanism: docking of regulatory complexes, like Blm3, PA28 or 19S, causes a conformational change of the N-terminal residues of the latent alpha-subunits, resulting in an activation of the proteolytically active sites. Archaebacterial CPs lack such regulatory gating mechanism. The controlled degradation of proteins by the proteasome dominates a variety of biological essential processes, like metabolic adaptation, apoptosis, inflammation, immune and stress response, as well as cell proliferation and cell differentiation. Selective and specific natural and synthetic inhibitors of CPs might find their practical application in treatment of cancer or inflammatory diseases.eng
dc.language.isoger
dc.publisherHumboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité
dc.subjectProteasomger
dc.subjectUbiquitinger
dc.subjectKristallstrukturger
dc.subjectProteaseger
dc.subjectProteinabbauger
dc.subjectProteasomeeng
dc.subjectUbiquitineng
dc.subjectCrystal structureeng
dc.subjectProteaseeng
dc.subjectprotein degradationeng
dc.subject.ddc610 Medizin
dc.titleStrukturelle und funktionelle Zusammenhänge und Unterschiede archaebakterieller und eukaryontischer 20S-Proteasome
dc.typedoctoralThesis
dc.identifier.urnurn:nbn:de:kobv:11-10035520
dc.identifier.urnurn:nbn:de:kobv:11-10039708
dc.identifier.urnurn:nbn:de:kobv:11-10039716
dc.identifier.doihttp://dx.doi.org/10.18452/13957
dc.identifier.alephidHU001149756
dc.date.accepted2004-11-22
dc.contributor.refereeHeinemann, Udo
dc.contributor.refereeSebald, Walter
dc.subject.dnb33 Medizin
local.edoc.pages62
local.edoc.type-nameHabilitationsschrift
local.edoc.institutionMedizinische Fakultät - Universitätsklinikum Charité

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