6id0

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Cryo-EM structure of a human intron lariat spliceosome prior to Prp43 loaded (ILS1 complex) at 2.9 angstrom resolution

Structural highlights

6id0 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.9Å
Experimental data:Check to display Experimental Data
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PRP8_HUMAN Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:600059. 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. RP13 inheritance is autosomal dominant.[1] [2] [:][3] [4]

Function

PRP8_HUMAN Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes.

Publication Abstract from PubMed

Pre-mRNA splicing is executed by the spliceosome, which has eight major functional states each with distinct composition. Five of these eight human spliceosomal complexes, all preceding exon ligation, have been structurally characterized. In this study, we report the cryo-electron microscopy structures of the human post-catalytic spliceosome (P complex) and intron lariat spliceosome (ILS) at average resolutions of 3.0 and 2.9 A, respectively. In the P complex, the ligated exon remains anchored to loop I of U5 small nuclear RNA, and the 3'-splice site is recognized by the junction between the 5'-splice site and the branch point sequence. The ATPase/helicase Prp22, along with the ligated exon and eight other proteins, are dissociated in the P-to-ILS transition. Intriguingly, the ILS complex exists in two distinct conformations, one with the ATPase/helicase Prp43 and one without. Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome disassembly.

Structures of the human spliceosomes before and after release of the ligated exon.,Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, Shi Y Cell Res. 2019 Feb 6. pii: 10.1038/s41422-019-0143-x. doi:, 10.1038/s41422-019-0143-x. PMID:30728453[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Pena V, Liu S, Bujnicki JM, Luhrmann R, Wahl MC. Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa. Mol Cell. 2007 Feb 23;25(4):615-24. PMID:17317632 doi:10.1016/j.molcel.2007.01.023
  2. ↑ McKie AB, McHale JC, Keen TJ, Tarttelin EE, Goliath R, van Lith-Verhoeven JJ, Greenberg J, Ramesar RS, Hoyng CB, Cremers FP, Mackey DA, Bhattacharya SS, Bird AC, Markham AF, Inglehearn CF. Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13). Hum Mol Genet. 2001 Jul 15;10(15):1555-62. PMID:11468273
  3. ↑ van Lith-Verhoeven JJ, van der Velde-Visser SD, Sohocki MM, Deutman AF, Brink HM, Cremers FP, Hoyng CB. Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13). Ophthalmic Genet. 2002 Mar;23(1):1-12. PMID:11910553
  4. ↑ Martinez-Gimeno M, Gamundi MJ, Hernan I, Maseras M, Milla E, Ayuso C, Garcia-Sandoval B, Beneyto M, Vilela C, Baiget M, Antinolo G, Carballo M. Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2003 May;44(5):2171-7. PMID:12714658
  5. ↑ Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, Shi Y. Structures of the human spliceosomes before and after release of the ligated exon. Cell Res. 2019 Feb 6. pii: 10.1038/s41422-019-0143-x. doi:, 10.1038/s41422-019-0143-x. PMID:30728453 doi:http://dx.doi.org/10.1038/s41422-019-0143-x

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6id0, resolution 2.90Å

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