3zio
minor-site specific NLS (A28)
Structural highlights
FunctionIMA1_MOUSE 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. Publication Abstract from PubMedNuclear localization signals (NLSs) contain one or two clusters of basic residues and are recognized by the import receptor importin-alpha. There are two NLS-binding sites (major and minor) on importin-alpha and the major NLS-binding site is considered to be the primary binding site. Here, we used crystallographic and biochemical methods to investigate the binding between importin-alpha and predicted "minor site-specific" NLSs: four peptide library-derived peptides, and the NLS from mouse RNA helicase II/Gualpha. The crystal structures reveal that these atypical NLSs indeed preferentially bind to the minor NLS-binding site. Unlike previously characterized NLSs, the C-terminal residues of these NLSs form an alpha-helical turn, stabilized by internal H-bond and cation-pi interactions between the aromatic residues from the NLSs and the positively-charged residues from importin-alpha. This helical turn sterically hinders binding at the major NLS-binding site, explaining the minor-site preference. Our data suggest the sequence RXXKR[K/X][F/Y/W]XXAF as the optimal minor NLS-binding site-specific motif, which may help identify novel proteins with atypical NLSs. Distinctive Conformation of Minor Site-Specific Nuclear Localization Signals Bound to Importin-alpha,Chang CW, Counago RM, Williams SJ, Boden M, Kobe B Traffic. 2013 Aug 2. doi: 10.1111/tra.12098. PMID:23910026[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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