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| | <StructureSection load='6s9i' size='340' side='right'caption='[[6s9i]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='6s9i' size='340' side='right'caption='[[6s9i]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6s9i]] 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=6S9I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S9I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6s9i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S9I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S9I FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNRNP200, ASCC3L1, HELIC2, KIAA0788 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRPF8, PRPC8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.598Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6s9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s9i OCA], [https://pdbe.org/6s9i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s9i RCSB], [https://www.ebi.ac.uk/pdbsum/6s9i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s9i ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6s9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s9i OCA], [http://pdbe.org/6s9i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s9i RCSB], [http://www.ebi.ac.uk/pdbsum/6s9i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s9i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/U520_HUMAN U520_HUMAN]] Retinitis pigmentosa. Retinitis pigmentosa 33 (RP33) [MIM:[http://omim.org/entry/610359 610359]]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. 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. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:16723661</ref> <ref>PMID:23045696</ref> <ref>PMID:19878916</ref> <ref>PMID:19710410</ref> <ref>PMID:21618346</ref> [[http://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN]] Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:[http://omim.org/entry/600059 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.<ref>PMID:17317632</ref> <ref>PMID:11468273</ref> [:]<ref>PMID:11910553</ref> <ref>PMID:12714658</ref> | + | [https://www.uniprot.org/uniprot/U520_HUMAN U520_HUMAN] Retinitis pigmentosa. Retinitis pigmentosa 33 (RP33) [MIM:[https://omim.org/entry/610359 610359]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. 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. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:16723661</ref> <ref>PMID:23045696</ref> <ref>PMID:19878916</ref> <ref>PMID:19710410</ref> <ref>PMID:21618346</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/U520_HUMAN U520_HUMAN]] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.<ref>PMID:16723661</ref> <ref>PMID:8670905</ref> <ref>PMID:9539711</ref> <ref>PMID:23045696</ref> [[http://www.uniprot.org/uniprot/PRP8_HUMAN 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. | + | [https://www.uniprot.org/uniprot/U520_HUMAN U520_HUMAN] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.<ref>PMID:16723661</ref> <ref>PMID:8670905</ref> <ref>PMID:9539711</ref> <ref>PMID:23045696</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6s9i" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6s9i" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Helicase 3D structures|Helicase 3D structures]] |
| | + | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RNA helicase]]
| + | [[Category: Santos KF]] |
| - | [[Category: Santos, K F]] | + | [[Category: Vester K]] |
| - | [[Category: Vester, K]] | + | [[Category: Wahl MC]] |
| - | [[Category: Wahl, M C]] | + | |
| - | [[Category: Dexd/h-box rna helicase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Pre-mrna splicing]]
| + | |
| - | [[Category: Rna and atp binding]]
| + | |
| - | [[Category: Rnp remodeling]]
| + | |
| - | [[Category: Spliceosome catalytic activation]]
| + | |
| Structural highlights
Disease
U520_HUMAN Retinitis pigmentosa. Retinitis pigmentosa 33 (RP33) [MIM:610359: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. 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. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] [2] [3] [4] [5]
Function
U520_HUMAN RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.[6] [7] [8] [9]
Publication Abstract from PubMed
The RNA helicase bad response to refrigeration 2 homolog (BRR2) is required for the activation of the spliceosome before the first catalytic step of RNA splicing. BRR2 represents a distinct subgroup of Ski2-like nucleic acid helicases whose members comprise tandem helicase cassettes. Only the N-terminal cassette of BRR2 is an active ATPase and can unwind substrate RNAs. The C-terminal cassette represents a pseudo-enzyme that can stimulate RNA-related activities of the N-terminal cassette. However, the molecular mechanisms by which the C-terminal cassette modulates the activities of the N-terminal unit remain elusive. Here, we show that N- and C-terminal cassettes adopt vastly different relative orientations in a crystal structure of BRR2 in complex with an activating domain of the spliceosomal Prp8 protein at 2.4 A resolution compared with the crystal structure of BRR2 alone. Likewise, inspection of BRR2 structures within spliceosomal complexes revealed that the cassettes occupy different relative positions and engage in different inter-cassette contacts during different splicing stages. Engineered disulfide bridges that locked the cassettes in two different relative orientations had opposite effects on the RNA unwinding activity of the N-terminal cassette, with one configuration enhancing and the other configuration inhibiting RNA unwinding compared with the unconstrained protein. Moreover, we found that differences in relative positioning of the cassettes strongly influence RNA-stimulated ATP hydrolysis by the N-terminal cassette. Our results indicate that the inactive C-terminal cassette of BRR2 can both positively and negatively affect the activity of the N-terminal helicase unit from a distance.
The inactive C-terminal cassette of the dual-cassette RNA helicase BRR2 both stimulates and inhibits the activity of the N-terminal helicase unit.,Vester K, Santos KF, Kuropka B, Weise C, Wahl MC J Biol Chem. 2019 Dec 30. pii: RA119.010964. doi: 10.1074/jbc.RA119.010964. PMID:31914407[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu S, Rauhut R, Vornlocher HP, Luhrmann R. The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA. 2006 Jul;12(7):1418-30. Epub 2006 May 24. PMID:16723661 doi:rna.55406
- ↑ Santos KF, Jovin SM, Weber G, Pena V, Luhrmann R, Wahl MC. Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome. Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045696 doi:10.1073/pnas.1208098109
- ↑ Zhao C, Bellur DL, Lu S, Zhao F, Grassi MA, Bowne SJ, Sullivan LS, Daiger SP, Chen LJ, Pang CP, Zhao K, Staley JP, Larsson C. Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs. Am J Hum Genet. 2009 Nov;85(5):617-27. Epub 2009 Oct 29. PMID:19878916 doi:S0002-9297(09)00455-8
- ↑ Li N, Mei H, MacDonald IM, Jiao X, Hejtmancik JF. Mutations in ASCC3L1 on 2q11.2 are associated with autosomal dominant retinitis pigmentosa in a Chinese family. Invest Ophthalmol Vis Sci. 2010 Feb;51(2):1036-43. doi: 10.1167/iovs.09-3725., Epub 2009 Aug 26. PMID:19710410 doi:10.1167/iovs.09-3725
- ↑ Benaglio P, McGee TL, Capelli LP, Harper S, Berson EL, Rivolta C. Next generation sequencing of pooled samples reveals new SNRNP200 mutations associated with retinitis pigmentosa. Hum Mutat. 2011 Jun;32(6):E2246-58. doi: 10.1002/humu.21485. Epub 2011 Feb 24. PMID:21618346 doi:10.1002/humu.21485
- ↑ Liu S, Rauhut R, Vornlocher HP, Luhrmann R. The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA. 2006 Jul;12(7):1418-30. Epub 2006 May 24. PMID:16723661 doi:rna.55406
- ↑ Lauber J, Fabrizio P, Teigelkamp S, Lane WS, Hartmann E, Luhrmann R. The HeLa 200 kDa U5 snRNP-specific protein and its homologue in Saccharomyces cerevisiae are members of the DEXH-box protein family of putative RNA helicases. EMBO J. 1996 Aug 1;15(15):4001-15. PMID:8670905
- ↑ Laggerbauer B, Achsel T, Luhrmann R. The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4188-92. PMID:9539711
- ↑ Santos KF, Jovin SM, Weber G, Pena V, Luhrmann R, Wahl MC. Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome. Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045696 doi:10.1073/pnas.1208098109
- ↑ Vester K, Santos KF, Kuropka B, Weise C, Wahl MC. The inactive C-terminal cassette of the dual-cassette RNA helicase BRR2 both stimulates and inhibits the activity of the N-terminal helicase unit. J Biol Chem. 2019 Dec 30. pii: RA119.010964. doi: 10.1074/jbc.RA119.010964. PMID:31914407 doi:http://dx.doi.org/10.1074/jbc.RA119.010964
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