3ul1
From Proteopedia
Mouse importin alpha: nucleoplasmin cNLS peptide complex
Structural highlights
Function[IMA2_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. [NUPL_XENLA] Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development. Nucleoplasmin is an acidic protein which is able to assemble nucleosomes by binding histones and transferring them to DNA. Publication Abstract from PubMedClassical nuclear localization signals (cNLSs), comprising one (monopartite cNLSs) or two clusters of basic residues connected by a 10-12 residue linker (bipartite cNLSs), are recognized by the nuclear import factor importin-alpha. The cNLSs bind along a concave groove on importin-alpha; however, specificity determinants of cNLSs remain poorly understood. We present a structural and interaction analysis study of importin-alpha binding to both designed and naturally occurring high-affinity cNLS-like sequences; the peptide inhibitors Bimax1 and Bimax2, and cNLS peptides of cap-binding protein 80. Our data suggest that cNLSs and cNLS-like sequences can achieve high affinity through maximizing interactions at the importin-alpha minor site, and by taking advantage of multiple linker region interactions. Our study defines an extended set of binding cavities on the importin-alpha surface, and also expands on recent observations that longer linker sequences are allowed, and that long-range electrostatic complementarity can contribute to cNLS-binding affinity. Altogether, our study explains the molecular and structural basis of the results of a number of recent studies, including systematic mutagenesis and peptide library approaches, and provides an improved level of understanding on the specificity determinants of a cNLS. Our results have implications for identifying cNLSs in novel proteins. Structural Basis of High-Affinity Nuclear Localization Signal Interactions with Importin-alpha,Marfori M, Lonhienne TG, Forwood JK, Kobe B Traffic. 2012 Jan 16. doi: 10.1111/j.1600-0854.2012.01329.x. PMID:22248489[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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