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6s8o

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Revision as of 10:31, 26 February 2020

Human Brr2 Helicase Region M641C/A1582C

Structural highlights

6s8o is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	SNRNP200, ASCC3L1, HELIC2, KIAA0788 (HUMAN)
Activity:	RNA helicase, with EC number 3.6.4.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6s8o"

@@ Line 3: / Line 3: @@
 <StructureSection load='6s8o' size='340' side='right'caption='[[6s8o]], [[Resolution|resolution]] 3.17&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6s8o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S8O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S8O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6s8o]] is a 1 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=6S8O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S8O FirstGlance]. <br>
-</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>
+</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])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6s8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s8o OCA], [http://pdbe.org/6s8o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s8o RCSB], [http://www.ebi.ac.uk/pdbsum/6s8o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s8o ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: RNA helicase]]

6s8o

From Proteopedia

Revision as of 10:31, 26 February 2020

Human Brr2 Helicase Region M641C/A1582C

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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