Monecke, Thomas

[["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.artnumber","e90915"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.lastpage","13"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Monecke, Thomas"],["dc.contributor.author","Buschmann, Juliane"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Wahle, Elmar"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:46:28Z"],["dc.date.available","2017-09-07T11:46:28Z"],["dc.date.issued","2014"],["dc.description.abstract","5'-nucleotidases catalyze the hydrolytic dephosphorylation of nucleoside monophosphates. As catabolic enzymes they contribute significantly to the regulation of cellular nucleotide levels; misregulation of nucleotide metabolism and nucleotidase deficiencies are associated with a number of diseases. The seven human 5'-nucleotidases differ with respect to substrate specificity and cellular localization. Recently, the novel cytosolic 5'-nucleotidase III-like protein, or cN-IIIB, has been characterized in human and Drosophila. cN-IIIB exhibits a strong substrate preference for the modified nucleotide 7-methylguanosine monophosphate but the structural reason for this preference was unknown. Here, we present crystal structures of cN-IIIB from Drosophila melanogaster bound to the reaction products 7-methylguanosine or cytidine. The structural data reveal that the cytosine-and 7-methylguanine moieties of the products are stacked between two aromatic residues in a coplanar but off-centered position. 7-methylguanosine is specifically bound through p-p interactions and distinguished from unmodified guanosine by additional cation-p coulomb interactions between the aromatic side chains and the positively charged 7-methylguanine. Notably, the base is further stabilized by T-shaped edge-to-face stacking of an additional tryptophan packing perpendicularly against the purine ring and forming, together with the other aromates, an aromatic slot. The structural data in combination with site-directed mutagenesis experiments reveal the molecular basis for the broad substrate specificity of cN-IIIB but also explain the substrate preference for 7-methylguanosine monophosphate. Analyzing the substrate specificities of cN-IIIB and the main pyrimidine 59-nucleotidase cN-IIIA by mutagenesis studies, we show that cN-IIIA dephosphorylates the purine m(7)GMP as well, hence redefining its substrate spectrum. Docking calculations with cN-IIIA and m(7)GMP as well as biochemical data reveal that Asn69 does not generally exclude the turnover of purine substrates thus correcting previous suggestions."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1371/journal.pone.0090915"],["dc.identifier.gro","3142174"],["dc.identifier.isi","000332483600105"],["dc.identifier.pmid","24603684"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10016"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5355"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Gottingen University; DFG"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Crystal Structures of the Novel Cytosolic 5'-Nucleotidase IIIB Explain Its Preference for m7GMP"],["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"]]