5tbk

Crystal structure of human importin a3 bound to RCC1

spinqualitylabelsall models 5tbk, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tbk is a 16 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 4pvz, 5t94 Gene: KPNA4, QIP1 (HUMAN), RCC1, CHC1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IMA3_HUMAN] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. [RCC1_HUMAN] Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP. Involved in the regulation of onset of chromosome condensation in the S phase. Binds both to the nucleosomes and double-stranded DNA. RCC1-Ran complex (together with other proteins) acts as a component of a signal transmission pathway that detects unreplicated DNA. Plays a key role in nucleo-cytoplasmic transport, mitosis and nuclear-envelope assembly. Publication Abstract from PubMed Active nuclear import of Ran exchange factor RCC1 is mediated by importin alpha3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin alpha3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin alpha1, although the two isoforms share an identical NLS-binding groove. Importin alpha3 uses its greater conformational flexibility to wedge the RCC1 beta-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing the beta-propeller, or inserting a linker between NLS and beta-propeller, disrupts specificity for importin alpha3, demonstrating the structural context rather than NLS sequence determines selectivity for isoform 3. We propose importin alpha3 evolved to recognize topologically complex NLSs that lie next to bulky domains or are masked by quaternary structures.Importin alpha3 facilitates the nuclear transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors reveal the molecular basis for the selectivity of RCC1 for importin alpha3 vs the generic importin alpha1 and discuss the evolution of importin alpha isoforms. Three-dimensional context rather than NLS amino acid sequence determines importin alpha subtype specificity for RCC1.,Sankhala RS, Lokareddy RK, Begum S, Pumroy RA, Gillilan RE, Cingolani G Nat Commun. 2017 Oct 17;8(1):979. doi: 10.1038/s41467-017-01057-7. PMID:29042532 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Importin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA