| Structural highlights
2ozb is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Related: | 1e7k |
| Gene: | NHP2L1 (Homo sapiens), PRPF31, PRP31 (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[PRP31_HUMAN] Defects in PRPF31 are the cause of retinitis pigmentosa type 11 (RP11) [MIM:600138]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP11 inheritance is autosomal dominant.[1] [2] [3] [4] [5]
Function
[PRP31_HUMAN] Involved in pre-mRNA splicing. Required for U4/U6.U5 tri-snRNP formation.[6] [NH2L1_HUMAN] Binds to the 5'-stem-loop of U4 snRNA and may play a role in the late stage of spliceosome assembly. The protein undergoes a conformational change upon RNA-binding.[7] [8]
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
Although highly homologous, the spliceosomal hPrp31 and the nucleolar Nop56 and Nop58 (Nop56/58) proteins recognize different ribonucleoprotein (RNP) particles. hPrp31 interacts with complexes containing the 15.5K protein and U4 or U4atac small nuclear RNA (snRNA), whereas Nop56/58 associate with 15.5K-box C/D small nucleolar RNA complexes. We present structural and biochemical analyses of hPrp31-15.5K-U4 snRNA complexes that show how the conserved Nop domain in hPrp31 maintains high RNP binding selectivity despite relaxed RNA sequence requirements. The Nop domain is a genuine RNP binding module, exhibiting RNA and protein binding surfaces. Yeast two-hybrid analyses suggest a link between retinitis pigmentosa and an aberrant hPrp31-hPrp6 interaction that blocks U4/U6-U5 tri-snRNP formation.
Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP.,Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Luhrmann R, Carlomagno T, Wahl MC Science. 2007 Apr 6;316(5821):115-20. PMID:17412961[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Luhrmann R, Carlomagno T, Wahl MC. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science. 2007 Apr 6;316(5821):115-20. PMID:17412961 doi:316/5821/115
- ↑ Deery EC, Vithana EN, Newbold RJ, Gallon VA, Bhattacharya SS, Warren MJ, Hunt DM, Wilkie SE. Disease mechanism for retinitis pigmentosa (RP11) caused by mutations in the splicing factor gene PRPF31. Hum Mol Genet. 2002 Dec 1;11(25):3209-19. PMID:12444105
- ↑ Vithana EN, Abu-Safieh L, Allen MJ, Carey A, Papaioannou M, Chakarova C, Al-Maghtheh M, Ebenezer ND, Willis C, Moore AT, Bird AC, Hunt DM, Bhattacharya SS. A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11). Mol Cell. 2001 Aug;8(2):375-81. PMID:11545739
- ↑ Al-Maghtheh M, Vithana E, Tarttelin E, Jay M, Evans K, Moore T, Bhattacharya S, Inglehearn CF. Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype. Am J Hum Genet. 1996 Oct;59(4):864-71. PMID:8808602
- ↑ Wang L, Ribaudo M, Zhao K, Yu N, Chen Q, Sun Q, Wang L, Wang Q. Novel deletion in the pre-mRNA splicing gene PRPF31 causes autosomal dominant retinitis pigmentosa in a large Chinese family. Am J Med Genet A. 2003 Sep 1;121A(3):235-9. PMID:12923864 doi:http://dx.doi.org/10.1002/ajmg.a.20224
- ↑ Makarova OV, Makarov EM, Liu S, Vornlocher HP, Luhrmann R. Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing. EMBO J. 2002 Mar 1;21(5):1148-57. PMID:11867543 doi:10.1093/emboj/21.5.1148
- ↑ Nottrott S, Hartmuth K, Fabrizio P, Urlaub H, Vidovic I, Ficner R, Luhrmann R. Functional interaction of a novel 15.5kD [U4/U6.U5] tri-snRNP protein with the 5' stem-loop of U4 snRNA. EMBO J. 1999 Nov 1;18(21):6119-33. PMID:10545122 doi:10.1093/emboj/18.21.6119
- ↑ Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Luhrmann R, Carlomagno T, Wahl MC. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science. 2007 Apr 6;316(5821):115-20. PMID:17412961 doi:316/5821/115
- ↑ Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Luhrmann R, Carlomagno T, Wahl MC. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science. 2007 Apr 6;316(5821):115-20. PMID:17412961 doi:316/5821/115
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