Structural highlights
Function
[IMA1_YEAST] Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Promotes docking of import substrates to the nuclear envelope. Seems to act as a cytosolic receptor for both simple and bipartite NLS motifs (By similarity).[1] [2] [3] [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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Karyopherin alpha (importin alpha) is an adaptor molecule that recognizes proteins containing nuclear localization signals (NLSs). The prototypical NLS that is able to bind to karyopherin alpha is that of the SV40 T antigen, and consists of a short positively charged sequence motif. Distinct classes of NLSs (monopartite and bipartite) have been identified that are only partly conserved with respect to one another but are nevertheless recognized by the same receptor. RESULTS: We report the crystal structures of two peptide complexes of yeast karyopherin alpha (Kapalpha): one with a human c-myc NLS peptide, determined at 2.1 A resolution, and one with a Xenopus nucleoplasmin NLS peptide, determined at 2.4 A resolution. Analysis of these structures reveals the determinants of specificity for the binding of a relatively hydrophobic monopartite NLS and of a bipartite NLS peptide. The peptides bind Kapalpha in its extended surface groove, which presents a modular array of tandem binding pockets for amino acid residues. CONCLUSIONS: Monopartite and bipartite NLSs bind to a different number of amino acid binding pockets and make different interactions within them. The relatively hydrophobic monopartite c-myc NLS binds extensively at a few binding pockets in a similar manner to that of the SV40 T antigen NLS. In contrast, the bipartite nucleoplasmin NLS engages the whole array of pockets with individually more limited but overall more abundant interactions, which include the NLS two basic clusters and the backbone of its non-conserved linker region. Versatility in the specific recognition of NLSs relies on the modular.
Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha.,Conti E, Kuriyan J Structure. 2000 Mar 15;8(3):329-38. PMID:10745017[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kussel P, Frasch M. Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis. Mol Gen Genet. 1995 Aug 21;248(3):351-63. PMID:7565597
- ↑ Tabb MM, Tongaonkar P, Vu L, Nomura M. Evidence for separable functions of Srp1p, the yeast homolog of importin alpha (Karyopherin alpha): role for Srp1p and Sts1p in protein degradation. Mol Cell Biol. 2000 Aug;20(16):6062-73. PMID:10913188
- ↑ Chen L, Romero L, Chuang SM, Tournier V, Joshi KK, Lee JA, Kovvali G, Madura K. Sts1 plays a key role in targeting proteasomes to the nucleus. J Biol Chem. 2011 Jan 28;286(4):3104-18. doi: 10.1074/jbc.M110.135863. Epub 2010 , Nov 12. PMID:21075847 doi:10.1074/jbc.M110.135863
- ↑ Conti E, Kuriyan J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure. 2000 Mar 15;8(3):329-38. PMID:10745017
