| Structural highlights
3uky is a 2 chain structure with sequence from Baker's yeast and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1ial, 3fex, 3fey, 3ukw, 3ukx, 3ukz, 3ul0, 3ul1 |
| Gene: | Kpna2 (LK3 transgenic mice), CBP80 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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. [NCBP1_YEAST] Component of the CBC complex, which binds co-transcriptionally to the 5'-cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs. The CBC complex is required for efficient pre-mRNA splicing through efficient commitment complex and spliceosome formation. Together with NPL3, the CBC complex is required for export of mRNAs out of the nucleus. The CBC complex is also involved in nuclear mRNA degradation, probably by directing the mRNAs to the sites of degradation. Affects replication of the positive-strand RNA virus BMV.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]
Publication Abstract from PubMed
Classical 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[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fortes P, Kufel J, Fornerod M, Polycarpou-Schwarz M, Lafontaine D, Tollervey D, Mattaj IW. Genetic and physical interactions involving the yeast nuclear cap-binding complex. Mol Cell Biol. 1999 Oct;19(10):6543-53. PMID:10490594
- ↑ Das B, Guo Z, Russo P, Chartrand P, Sherman F. The role of nuclear cap binding protein Cbc1p of yeast in mRNA termination and degradation. Mol Cell Biol. 2000 Apr;20(8):2827-38. PMID:10733586
- ↑ Shen EC, Stage-Zimmermann T, Chui P, Silver PA. 7The yeast mRNA-binding protein Npl3p interacts with the cap-binding complex. J Biol Chem. 2000 Aug 4;275(31):23718-24. PMID:10823828 doi:http://dx.doi.org/10.1074/jbc.M002312200
- ↑ Baron-Benhamou J, Fortes P, Inada T, Preiss T, Hentze MW. The interaction of the cap-binding complex (CBC) with eIF4G is dispensable for translation in yeast. RNA. 2003 Jun;9(6):654-62. PMID:12756324
- ↑ Das B, Butler JS, Sherman F. Degradation of normal mRNA in the nucleus of Saccharomyces cerevisiae. Mol Cell Biol. 2003 Aug;23(16):5502-15. PMID:12897126
- ↑ Kushner DB, Lindenbach BD, Grdzelishvili VZ, Noueiry AO, Paul SM, Ahlquist P. Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15764-9. Epub 2003 Dec 11. PMID:14671320 doi:10.1073/pnas.2536857100
- ↑ Uemura H, Jigami Y. GCR3 encodes an acidic protein that is required for expression of glycolytic genes in Saccharomyces cerevisiae. J Bacteriol. 1992 Sep;174(17):5526-32. PMID:1512188
- ↑ Gao Q, Das B, Sherman F, Maquat LE. Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4258-63. Epub 2005 Mar 7. PMID:15753296 doi:http://dx.doi.org/10.1073/pnas.0500684102
- ↑ Kuai L, Das B, Sherman F. A nuclear degradation pathway controls the abundance of normal mRNAs in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13962-7. Epub 2005 Sep 15. PMID:16166263 doi:http://dx.doi.org/10.1073/pnas.0506518102
- ↑ Lewis JD, Gorlich D, Mattaj IW. A yeast cap binding protein complex (yCBC) acts at an early step in pre-mRNA splicing. Nucleic Acids Res. 1996 Sep 1;24(17):3332-6. PMID:8811086
- ↑ Uemura H, Pandit S, Jigami Y, Sternglanz R. Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Genetics. 1996 Apr;142(4):1095-103. PMID:8846890
- ↑ Gorlich D, Kraft R, Kostka S, Vogel F, Hartmann E, Laskey RA, Mattaj IW, Izaurralde E. Importin provides a link between nuclear protein import and U snRNA export. Cell. 1996 Oct 4;87(1):21-32. PMID:8858145
- ↑ Shen EC, Henry MF, Weiss VH, Valentini SR, Silver PA, Lee MS. Arginine methylation facilitates the nuclear export of hnRNP proteins. Genes Dev. 1998 Mar 1;12(5):679-91. PMID:9499403
- ↑ Marfori M, Lonhienne TG, Forwood JK, Kobe B. Structural Basis of High-Affinity Nuclear Localization Signal Interactions with Importin-alpha Traffic. 2012 Jan 16. doi: 10.1111/j.1600-0854.2012.01329.x. PMID:22248489 doi:10.1111/j.1600-0854.2012.01329.x
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