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Publication Abstract from PubMed

Nuclear 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.