Monecke, Thomas

[["dc.bibliographiccitation.firstpage","s30"],["dc.bibliographiccitation.issue","a1"],["dc.bibliographiccitation.journal","Acta Crystallographica Section A Foundations and Advances"],["dc.bibliographiccitation.lastpage","s30"],["dc.bibliographiccitation.volume","72"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Port, Sarah A."],["dc.contributor.author","Weiß, Manfred S."],["dc.contributor.author","Kehlenbach, Ralph H."],["dc.contributor.author","Dickmanns, Achim"],["dc.date.accessioned","2020-12-10T18:26:02Z"],["dc.date.available","2020-12-10T18:26:02Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1107/S2053273316099526"],["dc.identifier.issn","2053-2733"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75925"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","final"],["dc.title","Crystal structure of the 239 kDa nuclear export complex CRM1 - RanGTP - Snurportin1 - Nup214 - MBP"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","960"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","965"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Haselbach, David"],["dc.contributor.author","Voss, Bela"],["dc.contributor.author","Russek, Andreas"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Thomson, Emma"],["dc.contributor.author","Hurt, Ed"],["dc.contributor.author","Zachariae, Ulrich"],["dc.contributor.author","Stark, Holger"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:48:18Z"],["dc.date.available","2017-09-07T11:48:18Z"],["dc.date.issued","2013"],["dc.description.abstract","In eukaryotes, the nucleocytoplasmic transport of macromolecules is mainly mediated by soluble nuclear transport receptors of the karyopherin-beta superfamily termed importins and exportins. The highly versatile exportin chromosome region maintenance 1 (CRM1) is essential for nuclear depletion of numerous structurally and functionally unrelated protein and ribonucleoprotein cargoes. CRM1 has been shown to adopt a toroidal structure in several functional transport complexes and was thought to maintain this conformation throughout the entire nucleocytoplasmic transport cycle. We solved crystal structures of free CRM1 from the thermophilic eukaryote Chaetomium thermophilum. Surprisingly, unbound CRM1 exhibits an overall extended and pitched superhelical conformation. The two regulatory regions, namely the acidic loop and the C-terminal a-helix, are dramatically repositioned in free CRM1 in comparison with the ternary CRM1-Ran-Snurportin1 export complex. Single-particle EM analysis demonstrates that, in a noncrystalline environment, free CRM1 exists in equilibrium between extended, superhelical and compact, ring-like conformations. Molecular dynamics simulations show that the C-terminal helix plays an important role in regulating the transition from an extended to a compact conformation and reveal how the binding site for nuclear export signals of cargoes is modulated by different CRM1 conformations. Combining these results, we propose a model for the cooperativity of CRM1 export complex assembly involving the long-range allosteric communication between the distant binding sites of GTP-bound Ran and cargo."],["dc.identifier.doi","10.1073/pnas.1215214110"],["dc.identifier.gro","3142406"],["dc.identifier.isi","000313909100042"],["dc.identifier.pmid","23277578"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7930"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","Structural basis for cooperativity of CRM1 export complex formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1481"],["dc.bibliographiccitation.journal","Acta Crystallographica Section F Structural Biology Communications"],["dc.bibliographiccitation.lastpage","1487"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Weiss, Manfred S."],["dc.contributor.author","Port, Sarah A."],["dc.contributor.author","Kehlenbach, Ralph H."],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:54:49Z"],["dc.date.available","2017-09-07T11:54:49Z"],["dc.date.issued","2015"],["dc.description.abstract","High conformational flexibility is an intrinsic and indispensable property of nuclear transport receptors, which makes crystallization and structure determination of macromolecular complexes containing exportins or importins particularly challenging. Here, the crystallization and structure determination of a quaternary nuclear export complex consisting of the exportin CRM1, the small GTPase Ran in its GTP-bound form, the export cargo SPN1 and an FG repeat-containing fragment of the nuclear pore complex component nucleoporin Nup214 fused to maltose-binding protein is reported. Optimization of constructs, seeding and the development of a sophisticated protocol including successive PEG-mediated crystal dehydration as well as additional post-mounting steps were essential to obtain well diffracting crystals."],["dc.identifier.doi","10.1107/S2053230X15021524"],["dc.identifier.gro","3141769"],["dc.identifier.isi","000369376500007"],["dc.identifier.pmid","26625290"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/868"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [Sonderforschungsbereich SFB860]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Int Union Crystallography"],["dc.relation.issn","2053-230X"],["dc.title","Combining dehydration, construct optimization and improved data collection to solve the crystal structure of a CRM1-RanGTP-SPN1-Nup214 quaternary nuclear export complex"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4179"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","FEBS Journal"],["dc.bibliographiccitation.lastpage","4194"],["dc.bibliographiccitation.volume","281"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:45:33Z"],["dc.date.available","2017-09-07T11:45:33Z"],["dc.date.issued","2014"],["dc.description.abstract","Nucleocytoplasmic trafficking in eukaryotic cells is a highly regulated and coordinated process which involves an increasing variety of soluble nuclear transport receptors. Generally, transport receptors specifically bind their cargo and facilitate its transition through nuclear pore complexes, aqueous channels connecting the two compartments. Directionality of such transport events by receptors of the importin beta superfamily requires the interaction with the small GTPase Ras-related nuclear antigen (Ran). While importins need RanGTP to release their cargo in the nucleus and thus to terminate import, exportins recruit cargo in the RanGTP-bound state. The exportin chromosome region maintenance 1 (CRM1) is a highly versatile transport receptor that exports a plethora of different protein and RNP cargoes. Moreover, binding of RanGTP and of cargo to CRM1 are highly cooperative events despite the fact that cargo and RanGTP do not interact directly in crystal structures of assembled export complexes. Integrative approaches have recently unraveled the individual steps of the CRM1 transport cycle at a structural level and explained how the HEAT-repeat architecture of CRM1 provides a framework for the key elements to mediate allosteric interactions with RanGTP, Ran binding proteins and cargo. Moreover, during the last decade, CRM1 has become a more and more appreciated target for anti-cancer drugs. Hence, detailed understanding of the flexibility, the regulatory features and the positive binding cooperativity between CRM1, Ran and cargo is a prerequisite for the development of highly effective drugs. Here we review recent structural advances in the characterization of CRM1 and CRM1-containing complexes with a special emphasis on X-ray crystallographic studies."],["dc.identifier.doi","10.1111/febs.12842"],["dc.identifier.gro","3142060"],["dc.identifier.isi","000342584200016"],["dc.identifier.pmid","24823279"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12823"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4100"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [Sonderforschungsbereich SFB860]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1742-4658"],["dc.relation.issn","1742-464X"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Allosteric control of the exportin CRM1 unraveled by crystal structure analysis"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","690"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","702"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Port, Sarah A."],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Spillner, Christiane"],["dc.contributor.author","Hofele, Romina"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Kehlenbach, Ralph H."],["dc.date.accessioned","2017-09-07T11:43:28Z"],["dc.date.available","2017-09-07T11:43:28Z"],["dc.date.issued","2015"],["dc.description.abstract","CRM1 is the major nuclear export receptor. During translocation through the nuclear pore, transport complexes transiently interact with phenylalanine-glycine (FG) repeats of multiple nucleoporins. On the cytoplasmic side of the nuclear pore, CRM1 tightly interacts with the nucleoporin Nup214. Here, we present the crystal structure of a 117-amino-acid FG-repeat-containing fragment of Nup214, in complex with CRM1, Snurportin 1, and RanGTP at 2.85 angstrom resolution. The structure reveals eight binding sites for Nup214 FG motifs on CRM1, with intervening stretches that are loosely attached to the transport receptor. Nup214 binds to N- and C-terminal regions of CRM1, thereby clamping CRM1 in a closed conformation and stabilizing the export complex. The role of conserved hydrophobic pockets for the recognition of FG motifs was analyzed in biochemical and cell-based assays. Comparative studies with RanBP3 and Nup62 shed light on specificities of CRM1-nucleoporin binding, which serves as a paradigm for transport receptor-nucleoporin interactions."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1016/j.celrep.2015.09.042"],["dc.identifier.gro","3141804"],["dc.identifier.isi","000363780900006"],["dc.identifier.pmid","26489467"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12544"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1257"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Structural and Functional Characterization of CRM1-Nup214 Interactions Reveals Multiple FG-Binding Sites Involved in Nuclear Export"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1087"],["dc.bibliographiccitation.issue","5930"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","1091"],["dc.bibliographiccitation.volume","324"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Guettler, Thomas"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Goerlich, Dirk"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:47:28Z"],["dc.date.available","2017-09-07T11:47:28Z"],["dc.date.issued","2009"],["dc.description.abstract","CRM1 mediates nuclear export of numerous unrelated cargoes, which may carry a short leucine-rich nuclear export signal or export signatures that include folded domains. How CRM1 recognizes such a variety of cargoes has been unknown up to this point. Here we present the crystal structure of the SPN1.CRM1.RanGTP export complex at 2.5 angstrom resolution (where SPN1 is snurportin1 and RanGTP is guanosine 5' triphosphate-bound Ran). SPN1 is a nuclear import adapter for cytoplasmically assembled, m(3)G-capped spliceosomal U snRNPs (small nuclear ribonucleoproteins). The structure shows how CRM1 can specifically return the cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes five hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal residues of SPN1. The structure suggests that RanGTP promotes cargo-binding to CRM1 solely through long-range conformational changes in the exportin."],["dc.identifier.doi","10.1126/science.1173388"],["dc.identifier.gro","3143116"],["dc.identifier.isi","000266246700046"],["dc.identifier.pmid","19389996"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/595"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Assoc Advancement Science"],["dc.relation.issn","0036-8075"],["dc.title","Crystal Structure of the Nuclear Export Receptor CRM1 in Complex with Snurportin1 and RanGTP"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1350"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Structure"],["dc.bibliographiccitation.lastpage","1360"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Doelker, Nicole"],["dc.contributor.author","Blanchet, Clement E."],["dc.contributor.author","Voss, Bela"],["dc.contributor.author","Haselbach, David"],["dc.contributor.author","Kappel, Christian"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Svergun, Dmitri I."],["dc.contributor.author","Stark, Holger"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Zachariae, Ulrich"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Dickmanns, Achim"],["dc.date.accessioned","2017-09-07T11:47:38Z"],["dc.date.available","2017-09-07T11:47:38Z"],["dc.date.issued","2013"],["dc.description.abstract","Proteins carrying nuclear export signals cooperatively assemble with the export factor CRM1 and the effector protein RanGTP. In lower eukaryotes, this cooperativity is coupled to CRM1 conformational changes; however, it is unknown if mammalian CRM1 maintains its compact conformation or shows similar structural flexibility. Here, combinations of small-angle X-ray solution scattering and electron microscopy experiments with molecular dynamics simulations reveal pronounced conformational flexibility in mammalian CRM1 and demonstrate that RanGTP binding induces association of its N- and C-terminal regions to form a toroid structure. The CRM1 toroid is stabilized mainly by local interactions between the terminal regions, rather than by global strain. The CRM1 acidic loop is key in transmitting the effect of this RanGTP-induced global conformational change to the NES-binding cleft by shifting its population to the open state, which displays enhanced cargo affinity. Cooperative CRM1 export complex assembly thus constitutes a highly dynamic process, encompassing an intricate interplay of global and local structural changes."],["dc.identifier.doi","10.1016/j.str.2013.05.015"],["dc.identifier.gro","3142310"],["dc.identifier.isi","000322927900011"],["dc.identifier.pmid","23850451"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6864"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0969-2126"],["dc.title","Structural Determinants and Mechanism of Mammalian CRM1 Allostery"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","538"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.lastpage","568"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:52:22Z"],["dc.date.available","2017-09-07T11:52:22Z"],["dc.date.issued","2015"],["dc.description.abstract","Recent studies have demonstrated the interference of nucleocytoplasmic trafficking with the establishment and maintenance of various cancers. Nucleocytoplasmic transport is highly regulated and coordinated, involving different nuclear transport factors or receptors, importins and exportins, that mediate cargo transport from the cytoplasm into the nucleus or the other way round, respectively. The exportin CRM1 (Chromosome region maintenance 1) exports a plethora of different protein cargoes and ribonucleoprotein complexes. Structural and biochemical analyses have enabled the deduction of individual steps of the CRM1 transport cycle. In addition, CRM1 turned out to be a valid target for anticancer drugs as it exports numerous proto-oncoproteins and tumor suppressors. Clearly, detailed understanding of the flexibility, regulatory features and cooperative binding properties of CRM1 for Ran and cargo is a prerequisite for the design of highly effective drugs. The first compound found to inhibit CRM1-dependent nuclear export was the natural drug Leptomycin B (LMB), which blocks export by competitively interacting with a highly conserved cleft on CRM1 required for nuclear export signal recognition. Clinical studies revealed serious side effects of LMB, leading to a search for alternative natural and synthetic drugs and hence a multitude of novel therapeutics. The present review examines recent progress in understanding the binding mode of natural and synthetic compounds and their inhibitory effects."],["dc.identifier.doi","10.3390/cells4030538"],["dc.identifier.gro","3144910"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2586"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","2073-4409"],["dc.title","Structural Basis of Targeting the Exportin CRM1 in Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","827"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.bibliographiccitation.lastpage","834"],["dc.bibliographiccitation.volume","382"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Schell, Stephanie"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:48:11Z"],["dc.date.available","2017-09-07T11:48:11Z"],["dc.date.issued","2008"],["dc.description.abstract","Poly(A)-specific ribonuclease (DARN) is a processive 3'-exoribonuclease involved in the decay of eukaryotic mRNAs. Interestingly, PARN interacts clot only with the 3' end of the mRNA but also with its 5' end as PARN contains an RRM domain that specifically binds both the poly(A) tail and the 7-methylguanosine (m(7)G) cap. The interaction of PARK with the 5' cap of mRNAs stimulates the deadenylation activity and enhances the processivity of this reaction. We have determined the crystal structure of the PARN-RRM domain with a bound m G triphosphate nucleotide, revealing a novel binding mode for the m7G cap. The structure of the m(7)G binding pocket is located outside of the canonical RNA-binding surface of the RRM domain and differs significantly from that of other m(7)G-cap-binding proteins. The crystal structure also shows a remarkable conformational flexibility of the RRM domain, leading to a perfect exchange of two alpha-helices with an adjacent protein molecule in the crystal lattice. (C) 2008 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.jmb.2008.07.073"],["dc.identifier.gro","3143224"],["dc.identifier.isi","000260024500001"],["dc.identifier.pmid","18694759"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/715"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd Elsevier Science Ltd"],["dc.relation.issn","0022-2836"],["dc.title","Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","s30"],["dc.bibliographiccitation.issue","a1"],["dc.bibliographiccitation.journal","Acta Crystallographica. Section A, Foundations and Advances"],["dc.bibliographiccitation.lastpage","s31"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Güttler, Thomas"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Doelker, Nicole"],["dc.contributor.author","Blanchet, Clement"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Görlich, Dirk"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Svergun, Dmitri"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2021-03-05T08:58:57Z"],["dc.date.available","2021-03-05T08:58:57Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1107/S0108767310099319"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80313"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0108-7673"],["dc.title","Structural basis for CRM1 nuclear export complex assembly"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]