4f93

From Proteopedia

(Difference between revisions)

Revision as of 04:42, 7 October 2022

Brr2 Helicase Region S1087L, Mg-ATP

Structural highlights

4f93 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
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

Assembly of a spliceosome, catalyzing precursor-messenger RNA splicing, involves multiple RNA-protein remodeling steps, driven by eight conserved DEXD/H-box RNA helicases. The 250-kDa Brr2 enzyme, which is essential for U4/U6 di-small nuclear ribonucleoprotein disruption during spliceosome catalytic activation and for spliceosome disassembly, is the only member of this group that is permanently associated with the spliceosome, thus requiring its faithful regulation. At the same time, Brr2 represents a unique subclass of superfamily 2 nucleic acid helicases, containing tandem helicase cassettes. Presently, the mechanistic and regulatory consequences of this unconventional architecture are unknown. Here we show that in human Brr2, two ring-like helicase cassettes intimately interact and functionally cooperate and how retinitis pigmentosa-linked Brr2 mutations interfere with the enzyme's function. Only the N-terminal cassette harbors ATPase and helicase activities in isolation. Comparison with other helicases and mutational analyses show how it threads single-stranded RNA, and structural features suggest how it can load onto an internal region of U4/U6 di-snRNA. Although the C-terminal cassette does not seem to engage RNA in the same fashion, it binds ATP and strongly stimulates the N-terminal helicase. Mutations at the cassette interface, in an intercassette linker or in the C-terminal ATP pocket, affect this cross-talk in diverse ways. Together, our results reveal the structural and functional interplay between two helicase cassettes in a tandem superfamily 2 enzyme and point to several sites through which Brr2 activity may be regulated.

Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome.,Santos KF, Jovin SM, Weber G, Pena V, Luhrmann R, Wahl MC Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045696^[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
↑ 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

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/4f93"

@@ Line 1: / Line 1: @@
 ==Brr2 Helicase Region S1087L, Mg-ATP==
-<StructureSection load='4f93' size='340' side='right' caption='[[4f93]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
+<StructureSection load='4f93' size='340' side='right'caption='[[4f93]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4f93]] 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=4F93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F93 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4f93]] is a 1 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=4F93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F93 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAN:SULFANILAMIDE'>SAN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAN:SULFANILAMIDE'>SAN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f91|4f91]], [[4f92|4f92]]</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=4f93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f93 OCA], [https://pdbe.org/4f93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f93 RCSB], [https://www.ebi.ac.uk/pdbsum/4f93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f93 ProSAT]</span></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=4f93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f93 OCA], [http://pdbe.org/4f93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f93 RCSB], [http://www.ebi.ac.uk/pdbsum/4f93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f93 ProSAT]</span></td></tr>
 </table>
 == 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>
+[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 ==
-[[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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: RNA helicase]]
+[[Category: Large Structures]]
-[[Category: Jovin, S M]]
+[[Category: Jovin SM]]
-[[Category: Luehrmann, R]]
+[[Category: Luehrmann R]]
-[[Category: Pena, V]]
+[[Category: Pena V]]
-[[Category: Santos, K F]]
+[[Category: Santos KF]]
-[[Category: Wahl, M C]]
+[[Category: Wahl MC]]
-[[Category: Weber, G]]
+[[Category: Weber G]]
-[[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]]

4f93

From Proteopedia

Revision as of 04:42, 7 October 2022

Brr2 Helicase Region S1087L, Mg-ATP

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox