Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Cyclin A/B1/B2 associated events during G2/M transition / Heme signaling / HuR (ELAVL1) binds and stabilizes mRNA / RNA import into nucleus / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Deactivation of the beta-catenin transactivating complex / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion ...Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Cyclin A/B1/B2 associated events during G2/M transition / Heme signaling / HuR (ELAVL1) binds and stabilizes mRNA / RNA import into nucleus / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Deactivation of the beta-catenin transactivating complex / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion / annulate lamellae / regulation of proteasomal ubiquitin-dependent protein catabolic process / RHO GTPases Activate Formins / Separation of Sister Chromatids / RNA cap binding / regulation of centrosome duplication / MAPK6/MAPK4 signaling / nuclear export signal receptor activity / snRNA import into nucleus / NLS-dependent protein nuclear import complex / regulation of protein export from nucleus / nuclear import signal receptor activity / regulation of protein catabolic process / protein localization to nucleus / ribosomal large subunit export from nucleus / ribosomal small subunit export from nucleus / Cajal body / mRNA export from nucleus / nuclear pore / protein export from nucleus / kinetochore / small GTPase binding / protein import into nucleus / snRNP Assembly / nuclear membrane / DNA-binding transcription factor binding / ribonucleoprotein complex / protein domain specific binding / nucleolus / negative regulation of transcription by RNA polymerase II / RNA binding / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function
Journal: Structure / Year: 2013 Title: Structural determinants and mechanism of mammalian CRM1 allostery. Authors: Nicole Dölker / Clement E Blanchet / Béla Voß / David Haselbach / Christian Kappel / Thomas Monecke / Dmitri I Svergun / Holger Stark / Ralf Ficner / Ulrich Zachariae / Helmut Grubmüller / Achim Dickmanns / 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 ...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.
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RNA cap binding / regulation of centrosome duplication / MAPK6/MAPK4 signaling / nuclear export signal receptor activity / snRNA import into nucleus / NLS-dependent protein nuclear import complex / regulation of protein export from nucleus / nuclear import signal receptor activity / regulation of protein catabolic process / protein localization to nucleus / 
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