Studienzentrum der Universitätsmedizin Göttingen

[["dc.bibliographiccitation.firstpage","307"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","319"],["dc.bibliographiccitation.volume","64"],["dc.contributor.author","Cretu, Constantin"],["dc.contributor.author","Schmitzova, Jana"],["dc.contributor.author","Ponce-Salvatierra, Almudena"],["dc.contributor.author","Dybkov, Olexandr"],["dc.contributor.author","De laurentiis, Evelina I."],["dc.contributor.author","Sharma, Kundan"],["dc.contributor.author","Will, Cindy L."],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Lührmann, Reinhard"],["dc.contributor.author","Pena, Vladimir"],["dc.date.accessioned","2018-11-07T10:06:55Z"],["dc.date.available","2018-11-07T10:06:55Z"],["dc.date.issued","2016"],["dc.description.abstract","SF3b is a heptameric protein complex of the U2 small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. Mutations in the largest SF3b subunit, SF3B1/SF3b155, are linked to cancer and lead to alternative branch site (BS) selection. Here we report the crystal structure of a human SF3b core complex, revealing how the distinctive conformation of SF3b155's HEAT domain is maintained by multiple contacts with SF3b130, SF3b10, and SF3b14b. Protein-protein crosslinking enabled the localization of the BS-binding proteins p14 and U2AF65 within SF3b155's HEAT-repeat superhelix, which together with SF3b14b forms a composite RNA-binding platform. SF3b155 residues, the mutation of which leads to cancer, contribute to the tertiary structure of the HEAT superhelix and its surface properties in the proximity of p14 and U2AF65. The molecular architecture of SF3b reveals the spatial organization of cancer-related SF3b155 mutations and advances our understanding of their effects on SF3b structure and function."],["dc.identifier.doi","10.1016/j.molcel.2016.08.036"],["dc.identifier.isi","000389515000011"],["dc.identifier.pmid","27720643"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39188"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1097-4164"],["dc.relation.issn","1097-2765"],["dc.title","Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","4491"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Cretu, Constantin"],["dc.contributor.author","Gee, Patricia"],["dc.contributor.author","Liu, Xiang"],["dc.contributor.author","Agrawal, Anant"],["dc.contributor.author","Nguyen, Tuong-Vi"],["dc.contributor.author","Ghosh, Arun K."],["dc.contributor.author","Cook, Andrew"],["dc.contributor.author","Jurica, Melissa"],["dc.contributor.author","Larsen, Nicholas A."],["dc.contributor.author","Pena, Vladimir"],["dc.date.accessioned","2021-09-01T06:42:23Z"],["dc.date.available","2021-09-01T06:42:23Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)—a complex chaperoning the selection of branch and 3′ splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept."],["dc.identifier.doi","10.1038/s41467-021-24741-1"],["dc.identifier.pii","24741"],["dc.identifier.pmid","34301950"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89042"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/328"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2041-1723"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.relation.workinggroup","RG Fernández-Busnadiego (Structural Cell Biology)"],["dc.rights","CC BY 4.0"],["dc.title","Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors"],["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","979"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","992.e6"],["dc.bibliographiccitation.volume","69"],["dc.contributor.author","de Moura, Tales Rocha"],["dc.contributor.author","Mozaffari-Jovin, Sina"],["dc.contributor.author","Szabó, Csaba Zoltán Kibédi"],["dc.contributor.author","Schmitzová, Jana"],["dc.contributor.author","Dybkov, Olexandr"],["dc.contributor.author","Cretu, Constantin"],["dc.contributor.author","Kachala, Michael"],["dc.contributor.author","Svergun, Dmitri"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Lührmann, Reinhard"],["dc.contributor.author","Pena, Vladimir"],["dc.date.accessioned","2020-12-10T15:20:22Z"],["dc.date.available","2020-12-10T15:20:22Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.molcel.2018.02.022"],["dc.identifier.issn","1097-2765"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72647"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Prp19/Pso4 Is an Autoinhibited Ubiquitin Ligase Activated by Stepwise Assembly of Three Splicing Factors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","265"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Cell"],["dc.bibliographiccitation.lastpage","273.e8"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Cretu, Constantin"],["dc.contributor.author","Agrawal, Anant A."],["dc.contributor.author","Cook, Andrew"],["dc.contributor.author","Will, Cindy L."],["dc.contributor.author","Fekkes, Peter"],["dc.contributor.author","Smith, Peter G."],["dc.contributor.author","Lührmann, Reinhard"],["dc.contributor.author","Larsen, Nicholas"],["dc.contributor.author","Buonamici, Silvia"],["dc.contributor.author","Pena, Vladimir"],["dc.date.accessioned","2022-11-07T07:41:02Z"],["dc.date.available","2022-11-07T07:41:02Z"],["dc.date.issued","2018"],["dc.description.abstract","SF3B is a multi-protein complex essential for branch site (BS) recognition and selection during pre-mRNA splicing. Several splicing modulators with antitumor activity bind SF3B and thereby modulate splicing. Here we report the crystal structure of a human SF3B core in complex with pladienolide B (PB), a macrocyclic splicing modulator and potent inhibitor of tumor cell proliferation. PB stalls SF3B in an open conformation by acting like a wedge within a hinge, modulating SF3B's transition to the closed conformation needed to form the BS adenosine-binding pocket and stably accommodate the BS/U2 duplex. This work explains the structural basis for the splicing modulation activity of PB and related compounds, and reveals key interactions between SF3B and a common pharmacophore, providing a framework for future structure-based drug design."],["dc.identifier.doi","10.1016/j.molcel.2018.03.011"],["dc.identifier.pmid","29656923"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116954"],["dc.language.iso","en"],["dc.relation.eissn","1097-4164"],["dc.relation.issn","1097-2765"],["dc.relation.orgunit","Max-Planck-Institut für biophysikalische Chemie"],["dc.title","Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]