Monecke, Thomas

[["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","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"]]

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[["dc.bibliographiccitation.firstpage","68a"],["dc.bibliographiccitation.issue","2, Supplement 1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","104"],["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","2018-05-28T11:48:46Z"],["dc.date.available","2018-05-28T11:48:46Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.bpj.2012.11.411"],["dc.identifier.uri","http://hdl.handle.net/2/14783"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Structural Determinants of Conformational Flexibility and Long-Range Allostery of the CRM1 Export Complex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]