| Structural highlights
Function
RCC1_YEAST Guanine nucleotide exchange factor that promotes the exchange of GSP1/GSP2-bound GDP by GTP and controls RNA metabolism and transport. Involved in yeast pheromone response pathway and in mRNA metabolism. Involved in nuclear pore complex (NPC) assembly and required for mRNA and ribosome nuclear export. Binds chromatin and is involved NPC-mediated transcriptional control.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
Active nuclear import of Ran exchange factor RCC1 is mediated by importin alpha3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin alpha3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin alpha1, although the two isoforms share an identical NLS-binding groove. Importin alpha3 uses its greater conformational flexibility to wedge the RCC1 beta-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing the beta-propeller, or inserting a linker between NLS and beta-propeller, disrupts specificity for importin alpha3, demonstrating the structural context rather than NLS sequence determines selectivity for isoform 3. We propose importin alpha3 evolved to recognize topologically complex NLSs that lie next to bulky domains or are masked by quaternary structures.Importin alpha3 facilitates the nuclear transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors reveal the molecular basis for the selectivity of RCC1 for importin alpha3 vs the generic importin alpha1 and discuss the evolution of importin alpha isoforms.
Three-dimensional context rather than NLS amino acid sequence determines importin alpha subtype specificity for RCC1.,Sankhala RS, Lokareddy RK, Begum S, Pumroy RA, Gillilan RE, Cingolani G Nat Commun. 2017 Oct 17;8(1):979. doi: 10.1038/s41467-017-01057-7. PMID:29042532[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Clark KL, Sprague GF Jr. Yeast pheromone response pathway: characterization of a suppressor that restores mating to receptorless mutants. Mol Cell Biol. 1989 Jun;9(6):2682-94. PMID:2548085
- ↑ Aebi M, Clark MW, Vijayraghavan U, Abelson J. A yeast mutant, PRP20, altered in mRNA metabolism and maintenance of the nuclear structure, is defective in a gene homologous to the human gene RCC1 which is involved in the control of chromosome condensation. Mol Gen Genet. 1990 Oct;224(1):72-80. PMID:2277633
- ↑ Clark KL, Ohtsubo M, Nishimoto T, Goebl M, Sprague GF Jr. The yeast SRM1 protein and human RCC1 protein share analogous functions. Cell Regul. 1991 Oct;2(10):781-92. PMID:1666302
- ↑ Fleischmann M, Clark MW, Forrester W, Wickens M, Nishimoto T, Aebi M. Analysis of yeast prp20 mutations and functional complementation by the human homologue RCC1, a protein involved in the control of chromosome condensation. Mol Gen Genet. 1991 Jul;227(3):417-23. PMID:1865879
- ↑ Forrester W, Stutz F, Rosbash M, Wickens M. Defects in mRNA 3'-end formation, transcription initiation, and mRNA transport associated with the yeast mutation prp20: possible coupling of mRNA processing and chromatin structure. Genes Dev. 1992 Oct;6(10):1914-26. PMID:1398069
- ↑ Amberg DC, Fleischmann M, Stagljar I, Cole CN, Aebi M. Nuclear PRP20 protein is required for mRNA export. EMBO J. 1993 Jan;12(1):233-41. PMID:7679070
- ↑ Kirkpatrick D, Solomon F. Overexpression of yeast homologs of the mammalian checkpoint gene RCC1 suppresses the class of alpha-tubulin mutations that arrest with excess microtubules. Genetics. 1994 Jun;137(2):381-92. PMID:8070652
- ↑ Hurt E, Hannus S, Schmelzl B, Lau D, Tollervey D, Simos G. A novel in vivo assay reveals inhibition of ribosomal nuclear export in ran-cycle and nucleoporin mutants. J Cell Biol. 1999 Feb 8;144(3):389-401. PMID:9971735
- ↑ Stage-Zimmermann T, Schmidt U, Silver PA. Factors affecting nuclear export of the 60S ribosomal subunit in vivo. Mol Biol Cell. 2000 Nov;11(11):3777-89. PMID:11071906
- ↑ Brodsky AS, Silver PA. Pre-mRNA processing factors are required for nuclear export. RNA. 2000 Dec;6(12):1737-49. PMID:11142374
- ↑ Baker RP, Harreman MT, Eccleston JF, Corbett AH, Stewart M. Interaction between Ran and Mog1 is required for efficient nuclear protein import. J Biol Chem. 2001 Nov 2;276(44):41255-62. Epub 2001 Aug 16. PMID:11509570 doi:10.1074/jbc.M106060200
- ↑ Clement M, Lavallee F, Barbes-Morin G, de Repentigny L, Belhumeur P. Overexpression of Bud5p can suppress mutations in the Gsp1p guanine nucleotide exchange factor Prp20p in Saccharomyces cerevisiae. Mol Genet Genomics. 2001 Sep;266(1):20-7. PMID:11589573
- ↑ Ryan KJ, McCaffery JM, Wente SR. The Ran GTPase cycle is required for yeast nuclear pore complex assembly. J Cell Biol. 2003 Mar 31;160(7):1041-53. Epub 2003 Mar 24. PMID:12654904 doi:10.1083/jcb.200209116
- ↑ Dilworth DJ, Tackett AJ, Rogers RS, Yi EC, Christmas RH, Smith JJ, Siegel AF, Chait BT, Wozniak RW, Aitchison JD. The mobile nucleoporin Nup2p and chromatin-bound Prp20p function in endogenous NPC-mediated transcriptional control. J Cell Biol. 2005 Dec 19;171(6):955-65. PMID:16365162 doi:10.1083/jcb.200509061
- ↑ Sankhala RS, Lokareddy RK, Begum S, Pumroy RA, Gillilan RE, Cingolani G. Three-dimensional context rather than NLS amino acid sequence determines importin alpha subtype specificity for RCC1. Nat Commun. 2017 Oct 17;8(1):979. doi: 10.1038/s41467-017-01057-7. PMID:29042532 doi:http://dx.doi.org/10.1038/s41467-017-01057-7
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