Schulten, Klaus

[["dc.bibliographiccitation.firstpage","7816"],["dc.bibliographiccitation.issue","28"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","7821"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Schweitzer, Andreas"],["dc.contributor.author","Aufderheide, Antje"],["dc.contributor.author","Rudack, Till"],["dc.contributor.author","Beck, Florian"],["dc.contributor.author","Pfeifer, Günter"],["dc.contributor.author","Plitzko, Jürgen M."],["dc.contributor.author","Sakata, Eri"],["dc.contributor.author","Schulten, Klaus"],["dc.contributor.author","Förster, Friedrich"],["dc.contributor.author","Baumeister, Wolfgang"],["dc.date.accessioned","2022-03-01T11:46:23Z"],["dc.date.available","2022-03-01T11:46:23Z"],["dc.date.issued","2016"],["dc.description.abstract","Protein degradation in eukaryotic cells is performed by the Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex consists of a core particle (CP) that proteolytically degrades polyubiquitylated proteins, and a regulatory particle (RP) containing the AAA-ATPase module. This module controls access to the proteolytic chamber inside the CP and is surrounded by non-ATPase subunits (Rpns) that recognize substrates and deubiquitylate them before unfolding and degradation. The architecture of the 26S holocomplex is highly conserved between yeast and humans. The structure of the human 26S holocomplex described here reveals previously unidentified features of the AAA-ATPase heterohexamer. One subunit, Rpt6, has ADP bound, whereas the other five have ATP in their binding pockets. Rpt6 is structurally distinct from the other five Rpt subunits, most notably in its pore loop region. For Rpns, the map reveals two main, previously undetected, features: the C terminus of Rpn3 protrudes into the mouth of the ATPase ring; and Rpn1 and Rpn2, the largest proteasome subunits, are linked by an extended connection. The structural features of the 26S proteasome observed in this study are likely to be important for coordinating the proteasomal subunits during substrate processing."],["dc.description.abstract","Protein degradation in eukaryotic cells is performed by the Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex consists of a core particle (CP) that proteolytically degrades polyubiquitylated proteins, and a regulatory particle (RP) containing the AAA-ATPase module. This module controls access to the proteolytic chamber inside the CP and is surrounded by non-ATPase subunits (Rpns) that recognize substrates and deubiquitylate them before unfolding and degradation. The architecture of the 26S holocomplex is highly conserved between yeast and humans. The structure of the human 26S holocomplex described here reveals previously unidentified features of the AAA-ATPase heterohexamer. One subunit, Rpt6, has ADP bound, whereas the other five have ATP in their binding pockets. Rpt6 is structurally distinct from the other five Rpt subunits, most notably in its pore loop region. For Rpns, the map reveals two main, previously undetected, features: the C terminus of Rpn3 protrudes into the mouth of the ATPase ring; and Rpn1 and Rpn2, the largest proteasome subunits, are linked by an extended connection. The structural features of the 26S proteasome observed in this study are likely to be important for coordinating the proteasomal subunits during substrate processing."],["dc.identifier.doi","10.1073/pnas.1608050113"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103654"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.rights.uri","http://www.pnas.org/preview_site/misc/userlicense.xhtml"],["dc.title","Structure of the human 26S proteasome at a resolution of 3.9 Å"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1305"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","1310"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Wehmer, Marc"],["dc.contributor.author","Rudack, Till"],["dc.contributor.author","Beck, Florian"],["dc.contributor.author","Aufderheide, Antje"],["dc.contributor.author","Pfeifer, Günter"],["dc.contributor.author","Plitzko, Jürgen M."],["dc.contributor.author","Förster, Friedrich"],["dc.contributor.author","Schulten, Klaus"],["dc.contributor.author","Baumeister, Wolfgang"],["dc.contributor.author","Sakata, Eri"],["dc.date.accessioned","2022-03-01T11:46:24Z"],["dc.date.available","2022-03-01T11:46:24Z"],["dc.date.issued","2017"],["dc.description.abstract","In eukaryotic cells, the ubiquitin–proteasome system (UPS) is responsible for the regulated degradation of intracellular proteins. The 26S holocomplex comprises the core particle (CP), where proteolysis takes place, and one or two regulatory particles (RPs). The base of the RP is formed by a heterohexameric AAA + ATPase module, which unfolds and translocates substrates into the CP. Applying single-particle cryo-electron microscopy (cryo-EM) and image classification to samples in the presence of different nucleotides and nucleotide analogs, we were able to observe four distinct conformational states (s1 to s4). The resolution of the four conformers allowed for the construction of atomic models of the AAA + ATPase module as it progresses through the functional cycle. In a hitherto unobserved state (s4), the gate controlling access to the CP is open. The structures described in this study allow us to put forward a model for the 26S functional cycle driven by ATP hydrolysis."],["dc.description.abstract","In eukaryotic cells, the ubiquitin–proteasome system (UPS) is responsible for the regulated degradation of intracellular proteins. The 26S holocomplex comprises the core particle (CP), where proteolysis takes place, and one or two regulatory particles (RPs). The base of the RP is formed by a heterohexameric AAA + ATPase module, which unfolds and translocates substrates into the CP. Applying single-particle cryo-electron microscopy (cryo-EM) and image classification to samples in the presence of different nucleotides and nucleotide analogs, we were able to observe four distinct conformational states (s1 to s4). The resolution of the four conformers allowed for the construction of atomic models of the AAA + ATPase module as it progresses through the functional cycle. In a hitherto unobserved state (s4), the gate controlling access to the CP is open. The structures described in this study allow us to put forward a model for the 26S functional cycle driven by ATP hydrolysis."],["dc.identifier.doi","10.1073/pnas.1621129114"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103655"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.rights.uri","http://www.pnas.org/site/misc/userlicense.xhtml"],["dc.title","Structural insights into the functional cycle of the ATPase module of the 26S proteasome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]