Dienemann, Christian

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Frieg, Benedikt"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Geraets, James A."],["dc.contributor.author","Najbauer, Eszter E."],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Andreas, Loren B."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Schröder, Gunnar F."],["dc.date.accessioned","2022-12-01T08:30:50Z"],["dc.date.available","2022-12-01T08:30:50Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n α-synuclein misfolding and aggregation into fibrils is a common feature of α-synucleinopathies, such as Parkinson’s disease, in which α-synuclein fibrils are a characteristic hallmark of neuronal inclusions called Lewy bodies. Studies on the composition of Lewy bodies extracted postmortem from brain tissue of Parkinson’s patients revealed that lipids and membranous organelles are also a significant component. Interactions between α-synuclein and lipids have been previously identified as relevant for Parkinson’s disease pathology, however molecular insights into their interactions have remained elusive. Here we present cryo-electron microscopy structures of six α-synuclein fibrils in complex with lipids, revealing specific lipid-fibril interactions. We observe that phospholipids promote an alternative protofilament fold, mediate an unusual arrangement of protofilaments, and fill the central cavities of the fibrils. Together with our previous studies, these structures also indicate a mechanism for fibril-induced lipid extraction, which is likely to be involved in the development of α-synucleinopathies. Specifically, one potential mechanism for the cellular toxicity is the disruption of intracellular vesicles mediated by fibrils and oligomers, and therefore the modulation of these interactions may provide a promising strategy for future therapeutic interventions."],["dc.identifier.doi","10.1038/s41467-022-34552-7"],["dc.identifier.pii","34552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117993"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The 3D structure of lipidic fibrils of α-synuclein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","353"],["dc.bibliographiccitation.issue","7603"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","358"],["dc.bibliographiccitation.volume","533"],["dc.contributor.author","Plaschka, Clemens"],["dc.contributor.author","Hantsche, M."],["dc.contributor.author","Dienemann, C."],["dc.contributor.author","Burzinski, C."],["dc.contributor.author","Plitzko, Juergen"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2017-09-07T11:44:54Z"],["dc.date.available","2017-09-07T11:44:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 angstrom and 3.6 angstrom, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts."],["dc.identifier.doi","10.1038/nature17990"],["dc.identifier.gro","3141685"],["dc.identifier.isi","000376004300040"],["dc.identifier.pmid","27193681"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8883"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.title","Transcription initiation complex structures elucidate DNA opening"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.contributor.author","Rengachari, Srinivasan"],["dc.contributor.author","Schilbach, Sandra"],["dc.contributor.author","Kaliyappan, Thangavelu"],["dc.contributor.author","Gouge, Jerome"],["dc.contributor.author","Zumer, Kristina"],["dc.contributor.author","Schwarz, Juliane"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Vannini, Alessandro"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-12-01T08:30:54Z"],["dc.date.available","2022-12-01T08:30:54Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n RNA polymerase II (Pol II) carries out transcription of both protein-coding and non-coding genes. Whereas Pol II initiation at protein-coding genes has been studied in detail, Pol II initiation at non-coding genes, such as small nuclear RNA (snRNA) genes, is less well understood at the structural level. Here, we study Pol II initiation at snRNA gene promoters and show that the snRNA-activating protein complex (SNAPc) enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro. We then resolve cryo-EM structures of the SNAPc-containing Pol IIpre-initiation complex (PIC) assembled on U1 and U5 snRNA promoters. The core of SNAPc binds two turns of DNA and recognizes the snRNA promoter-specific proximal sequence element (PSE), located upstream of the TATA box-binding protein TBP. Two extensions of SNAPc, called wing-1 and wing-2, bind TFIIA and TFIIB, respectively, explaining how SNAPc directs Pol II to snRNA promoters. Comparison of structures of closed and open promoter complexes elucidates TFIIH-independent DNA opening. These results provide the structural basis of Pol II initiation at non-coding RNA gene promoters."],["dc.identifier.doi","10.1038/s41594-022-00857-w"],["dc.identifier.pii","857"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118010"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Structural basis of SNAPc-dependent snRNA transcription initiation by RNA polymerase II"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Communications Biology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Frieg, Benedikt"],["dc.contributor.author","Geraets, James A."],["dc.contributor.author","Strohäker, Timo"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Mavroeidi, Panagiota"],["dc.contributor.author","Jung, Byung Chul"],["dc.contributor.author","Kim, Woojin S."],["dc.contributor.author","Lee, Seung-Jae"],["dc.contributor.author","Xilouri, Maria"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Schröder, Gunnar F."],["dc.date.accessioned","2022-11-01T10:16:46Z"],["dc.date.available","2022-11-01T10:16:46Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are progressive and unremitting neurological diseases that are neuropathologically characterized by α-synuclein inclusions. Increasing evidence supports the aggregation of α-synuclein in specific brain areas early in the disease course, followed by the spreading of α-synuclein pathology to multiple brain regions. However, little is known about how the structure of α-synuclein fibrils influence its ability to seed endogenous α-synuclein in recipient cells. Here, we aggregated α-synuclein by seeding with homogenates of PD- and MSA-confirmed brain tissue, determined the resulting α-synuclein fibril structures by cryo-electron microscopy, and characterized their seeding potential in mouse primary oligodendroglial cultures. The combined analysis shows that the two patient material-amplified α-synuclein fibrils share a similar protofilament fold but differ in their inter-protofilament interface and their ability to recruit endogenous α-synuclein. Our study indicates that the quaternary structure of α-synuclein fibrils modulates the seeding of α-synuclein pathology inside recipient cells. It thus provides an important advance in the quest to understand the connection between the structure of α-synuclein fibrils, cellular seeding/spreading, and ultimately the clinical manifestations of different synucleinopathies."],["dc.identifier.doi","10.1038/s42003-022-03948-y"],["dc.identifier.pii","3948"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116649"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.relation.eissn","2399-3642"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","448"],["dc.bibliographiccitation.issue","7799"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","451"],["dc.bibliographiccitation.volume","579"],["dc.contributor.author","Wagner, Felix R."],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Wang, Haibo"],["dc.contributor.author","Stützer, Alexandra"],["dc.contributor.author","Tegunov, Dimitry"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-04-14T08:27:11Z"],["dc.date.available","2021-04-14T08:27:11Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41586-020-2088-0"],["dc.identifier.pmid","32188943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82197"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/193"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.relation.workinggroup","RG Cramer"],["dc.title","Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Dervişoğlu, Rıza"],["dc.contributor.author","Frieg, Benedikt"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Nimerovsky, Evgeny"],["dc.contributor.author","Sant, Vrinda"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Andreas, Loren B."],["dc.date.accessioned","2022-10-04T10:21:08Z"],["dc.date.available","2022-10-04T10:21:08Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Aggregation of amyloidogenic proteins is a characteristic of multiple neurodegenerative diseases. Atomic resolution of small molecule binding to such pathological protein aggregates is of interest for the development of therapeutics and diagnostics. Here we investigate the interaction between α-synuclein fibrils and anle138b, a clinical drug candidate for disease modifying therapy in neurodegeneration and a promising scaffold for positron emission tomography tracer design. We used nuclear magnetic resonance spectroscopy and the cryogenic electron microscopy structure of α-synuclein fibrils grown in the presence of lipids to locate anle138b within a cavity formed between two β-strands. We explored and quantified multiple binding modes of the compound in detail using molecular dynamics simulations. Our results reveal stable polar interactions between anle138b and backbone moieties inside the tubular cavity of the fibrils. Such cavities are common in other fibril structures as well."],["dc.identifier.doi","10.1038/s41467-022-32797-w"],["dc.identifier.pii","32797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114336"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","97"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","106.e4"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Schwalb, Björn"],["dc.contributor.author","Schilbach, Sandra"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-03-01T11:45:17Z"],["dc.date.available","2022-03-01T11:45:17Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.molcel.2018.10.014"],["dc.identifier.pii","S1097276518308463"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103276"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","1097-2765"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Promoter Distortion and Opening in the RNA Polymerase II Cleft"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1525"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","1536"],["dc.bibliographiccitation.volume","179"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Bartuli, Julia"],["dc.contributor.author","Grimm, Clemens"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Bedenk, Kristina"],["dc.contributor.author","Szalay, Aladar A"],["dc.contributor.author","Fischer, Utz"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2020-04-02T14:06:45Z"],["dc.date.available","2020-04-02T14:06:45Z"],["dc.date.issued","2019-12-12"],["dc.description.abstract","Poxviruses use virus-encoded multisubunit RNA polymerases (vRNAPs) and RNA-processing factors to generate m7G-capped mRNAs in the host cytoplasm. In the accompanying paper, we report structures of core and complete vRNAP complexes of the prototypic Vaccinia poxvirus (Grimm et al., 2019; in this issue of Cell). Here, we present the cryo-electron microscopy (cryo-EM) structures of Vaccinia vRNAP in the form of a transcribing elongation complex and in the form of a co-transcriptional capping complex that contains the viral capping enzyme (CE). The trifunctional CE forms two mobile modules that bind the polymerase surface around the RNA exit tunnel. RNA extends from the vRNAP active site through this tunnel and into the active site of the CE triphosphatase. Structural comparisons suggest that growing RNA triggers large-scale rearrangements on the surface of the transcription machinery during the transition from transcription initiation to RNA capping and elongation. Our structures unravel the basis for synthesis and co-transcriptional modification of poxvirus RNA."],["dc.identifier.doi","10.1016/j.cell.2019.11.023"],["dc.identifier.pmid","31835031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63541"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/32"],["dc.language.iso","en"],["dc.notes","Research funded by Deutsche Forschungsgemeinschaft | Volkswagen Foundation | Excellence Strategy (EXC 2067/1- 390729940) | European Research Council Advanced Investigator Grant TRANSREGULON (693023)"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1097-4172"],["dc.relation.issn","0092-8674"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.title","Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","883"],["dc.bibliographiccitation.issue","6569"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","887"],["dc.bibliographiccitation.volume","374"],["dc.contributor.author","Fianu, Isaac"],["dc.contributor.author","Chen, Ying"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Dybkov, Olexandr"],["dc.contributor.author","Linden, Andreas"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-12-01T09:21:16Z"],["dc.date.available","2021-12-01T09:21:16Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1126/science.abk0154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94392"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/359"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1095-9203"],["dc.relation.issn","0036-8075"],["dc.relation.workinggroup","RG Cramer"],["dc.title","Structural basis of Integrator-mediated transcription regulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","204"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","209"],["dc.bibliographiccitation.volume","551"],["dc.contributor.author","Schilbach, S."],["dc.contributor.author","Hantsche, M."],["dc.contributor.author","Tegunov, D."],["dc.contributor.author","Dienemann, C."],["dc.contributor.author","Wigge, C."],["dc.contributor.author","Urlaub, H."],["dc.contributor.author","Cramer, P."],["dc.date.accessioned","2018-01-09T12:04:30Z"],["dc.date.available","2018-01-09T12:04:30Z"],["dc.date.issued","2017"],["dc.description.abstract","For the initiation of transcription, RNA polymerase II (Pol II) assembles with general transcription factors on promoter DNA to form the pre-initiation complex (PIC). Here we report cryo-electron microscopy structures of the Saccharomyces cerevisiae PIC and PIC-core Mediator complex at nominal resolutions of 4.7 Å and 5.8 Å, respectively. The structures reveal transcription factor IIH (TFIIH), and suggest how the core and kinase TFIIH modules function in the opening of promoter DNA and the phosphorylation of Pol II, respectively. The TFIIH core subunit Ssl2 (a homologue of human XPB) is positioned on downstream DNA by the 'E-bridge' helix in TFIIE, consistent with TFIIE-stimulated DNA opening. The TFIIH kinase module subunit Tfb3 (MAT1 in human) anchors the kinase Kin28 (CDK7), which is mobile in the PIC but preferentially located between the Mediator hook and shoulder in the PIC-core Mediator complex. Open spaces between the Mediator head and middle modules may allow access of the kinase to its substrate, the C-terminal domain of Pol II."],["dc.identifier.doi","10.1038/nature24282"],["dc.identifier.pmid","29088706"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11583"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1476-4687"],["dc.title","Structures of transcription pre-initiation complex with TFIIH and Mediator"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]