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.journal","Nature Structural & Molecular Biology"],["dc.contributor.author","Kabinger, Florian"],["dc.contributor.author","Stiller, Carina"],["dc.contributor.author","Schmitzová, Jana"],["dc.contributor.author","Dienemann, C."],["dc.contributor.author","Kokic, Goran"],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Höbartner, Claudia"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2021-09-01T06:42:22Z"],["dc.date.available","2021-09-01T06:42:22Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β- d - N 4 -hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir."],["dc.identifier.doi","10.1038/s41594-021-00651-0"],["dc.identifier.pii","651"],["dc.identifier.pmid","34381216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89038"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/381"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/171"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/28"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | St01: Structure and distribution of ribosomes at the inner mitochondrial membrane"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.rights","CC BY 4.0"],["dc.title","Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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.firstpage","493"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","501"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Dombrowski, Marco"],["dc.contributor.author","Engeholm, Maik"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Dodonova, Svetlana"],["dc.contributor.author","Cramer, Patrick"],["dc.date.accessioned","2022-06-01T09:39:10Z"],["dc.date.available","2022-06-01T09:39:10Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Throughout the genome, nucleosomes often form regular arrays that differ in nucleosome repeat length (NRL), occupancy of linker histone H1 and transcriptional activity. Here, we report cryo-EM structures of human H1-containing tetranucleosome arrays with four physiologically relevant NRLs. The structures show a zig-zag arrangement of nucleosomes, with nucleosomes 1 and 3 forming a stack. H1 binding to stacked nucleosomes depends on the NRL, whereas H1 always binds to the non-stacked nucleosomes 2 and 4. Short NRLs lead to altered trajectories of linker DNA, and these altered trajectories sterically impair H1 binding to the stacked nucleosomes in our structures. As the NRL increases, linker DNA trajectories relax, enabling H1 contacts and binding. Our results provide an explanation for why arrays with short NRLs are depleted of H1 and suited for transcription, whereas arrays with long NRLs show full H1 occupancy and can form transcriptionally silent heterochromatin regions."],["dc.identifier.doi","10.1038/s41594-022-00768-w"],["dc.identifier.pii","768"],["dc.identifier.pmid","35581345"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108404"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/531"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.relation.workinggroup","RG Cramer"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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","713"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Structural & Molecular Biology"],["dc.bibliographiccitation.lastpage","723"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Bhatta, Arjun"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Cramer, Patrick"],["dc.contributor.author","Hillen, Hauke S."],["dc.date.accessioned","2021-10-01T09:57:57Z"],["dc.date.available","2021-10-01T09:57:57Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry out RNA cleavage and methylation by unknown mechanisms. Here, we present the cryo-EM structure of human mtRNase P bound to precursor tRNA, which reveals a unique mechanism of substrate recognition and processing. Subunits TRMT10C and SDR5C1 form a subcomplex that binds conserved mitochondrial tRNA elements, including the anticodon loop, and positions the tRNA for methylation. The endonuclease PRORP is recruited and activated through interactions with its PPR and nuclease domains to ensure precise pre-tRNA cleavage. The structure provides the molecular basis for the first step of RNA processing in human mitochondria."],["dc.identifier.doi","10.1038/s41594-021-00637-y"],["dc.identifier.pii","637"],["dc.identifier.pmid","34489609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89952"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/337"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/154"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/9"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | St01: Structure and distribution of ribosomes at the inner mitochondrial membrane"],["dc.relation.eissn","1545-9985"],["dc.relation.issn","1545-9993"],["dc.relation.workinggroup","RG Cramer"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.rights","CC BY 4.0"],["dc.title","Structural basis of RNA processing by human mitochondrial RNase P"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]