7w5b | pdb_00007w5b

The cryo-EM structure of human C* complex

Structural highlights

7w5b is a 10 chain structure with sequence from Homo sapiens and Unidentified adenovirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.3Å
Ligands:	ATP, GTP, IHP, MG, SEP, ZN
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 involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C( *) complex, which executes exon ligation. Here, we report cryo-EM structures of two intermediate human spliceosomal complexes, pre-C( *)-I and pre-C( *)-II, both at 3.6 A. In both structures, the 3' splice site is already docked into the active site, the ensuing 3' exon sequences are anchored on PRP8, and the step II factor FAM192A contacts the duplex between U2 snRNA and the branch site. In the transition of pre-C( *)-I to pre-C( *)-II, the step II factors Cactin, FAM32A, PRKRIP1, and SLU7 are recruited. Notably, the RNA helicase PRP22 is positioned quite differently in the pre-C( *)-I, pre-C( *)-II, and C( *) complexes, suggesting a role in 3' exon binding and proofreading. Together with information on human C and C( *) complexes, our studies recapitulate a molecular choreography of the C-to-C( *) transition, revealing mechanistic insights into exon ligation.

Mechanism of exon ligation by human spliceosome.,Zhan X, Lu Y, Zhang X, Yan C, Shi Y Mol Cell. 2022 Aug 4;82(15):2769-2778.e4. doi: 10.1016/j.molcel.2022.05.021. Epub , 2022 Jun 14. PMID:35705093^[5]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ Zhan X, Lu Y, Zhang X, Yan C, Shi Y. Mechanism of exon ligation by human spliceosome. Mol Cell. 2022 Aug 4;82(15):2769-2778.e4. PMID:35705093 doi:10.1016/j.molcel.2022.05.021

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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] Zhan X, Lu Y, Zhang X, Yan C, Shi Y. Mechanism of exon ligation by human spliceosome. Mol Cell. 2022 Aug 4;82(15):2769-2778.e4. PMID:35705093 doi:10.1016/j.molcel.2022.05.021

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7w5b | pdb_00007w5b

The cryo-EM structure of human C* complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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