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4jka

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Revision as of 15:57, 20 November 2019

Open and closed forms of R1865A human PRP8 RNase H-like domain with bound Co ion

Structural highlights

4jka is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3enb, 4jk7, 4jk8, 4jk9, 4jkb, 4jkc, 4jkd, 4jke, 4jkf, 4jkg, 4jkh
Gene:	PRP8, PRPC8, PRPF8 (HUMAN)
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

Splicing of pre-mRNAs in eukaryotes is catalyzed by the spliceosome, a large RNA-protein metalloenzyme. The catalytic center of the spliceosome involves a structure comprising the U2 and U6 snRNAs and includes a metal bound by U6 snRNA. The precise architecture of the splicesome active site, however, and the question of whether it includes protein components, remains unresolved. A wealth of evidence places the protein PRP8 at the heart of the spliceosome through assembly and catalysis. Here we provide evidence that the RNase H domain of PRP8 undergoes a conformational switch between the two steps of splicing, rationalizing yeast prp8 alleles that promote either the first or second step. We also show that this switch unmasks a metal-binding site involved in the second step. Together, these data establish that PRP8 is a metalloprotein that promotes exon ligation within the spliceosome.

A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation.,Schellenberg MJ, Wu T, Ritchie DB, Fica S, Staley JP, Atta KA, Lapointe P, Macmillan AM Nat Struct Mol Biol. 2013 May 19. doi: 10.1038/nsmb.2556. PMID:23686287^[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
↑ Schellenberg MJ, Wu T, Ritchie DB, Fica S, Staley JP, Atta KA, Lapointe P, Macmillan AM. A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation. Nat Struct Mol Biol. 2013 May 19. doi: 10.1038/nsmb.2556. PMID:23686287 doi:10.1038/nsmb.2556

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4jka"

@@ Line 1: / Line 1: @@
 ==Open and closed forms of R1865A human PRP8 RNase H-like domain with bound Co ion==
-<StructureSection load='4jka' size='340' side='right' caption='[[4jka]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
+<StructureSection load='4jka' size='340' side='right'caption='[[4jka]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4jka]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JKA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JKA FirstGlance]. <br>
@@ Line 30: / Line 30: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Atta, K A]]
 [[Category: MacMillan, A M]]

4jka

From Proteopedia

Revision as of 15:57, 20 November 2019

Open and closed forms of R1865A human PRP8 RNase H-like domain with bound Co ion

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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