5m5p

From Proteopedia

(Difference between revisions)

Revision as of 06:34, 16 October 2019

S. cerevisiae spliceosomal helicase Brr2 (271-end) in complex with the Jab/MPN domain of S. cerevisiae Prp8

Structural highlights

5m5p is a 4 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	BRR2, RSS1, SNU246, YER172C, SYGP-ORF66 (Baker's yeast), PRP8, DBF3, DNA39, RNA8, SLT21, USA2, YHR165C (Baker's yeast)
Activity:	RNA helicase, with EC number 3.6.4.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BRR2_YEAST] 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.^[1] ^[2] ^[3] ^[4] [PRP8_YEAST] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

RNA helicase Brr2 is implicated in multiple phases of pre-mRNA splicing and thus requires tight regulation. Brr2 can be auto-inhibited via a large N-terminal region folding back onto its helicase core and auto-activated by a catalytically inactive C-terminal helicase cassette. Furthermore, it can be regulated in trans by the Jab1 domain of the Prp8 protein, which can inhibit Brr2 by intermittently inserting a C-terminal tail in the enzyme's RNA-binding tunnel or activate the helicase after removal of this tail. Presently it is unclear, whether these regulatory mechanisms functionally interact and to which extent they are evolutionarily conserved. Here, we report crystal structures of Saccharomyces cerevisiae and Chaetomium thermophilum Brr2-Jab1 complexes, demonstrating that Jab1-based inhibition of Brr2 presumably takes effect in all eukaryotes but is implemented via organism-specific molecular contacts. Moreover, the structures show that Brr2 auto-inhibition can act in concert with Jab1-mediated inhibition, and suggest that the N-terminal region influences how the Jab1 C-terminal tail interacts at the RNA-binding tunnel. Systematic RNA binding and unwinding studies revealed that the N-terminal region and the Jab1 C-terminal tail specifically interfere with accommodation of double-stranded and single-stranded regions of an RNA substrate, respectively, mutually reinforcing each other. Additionally, such analyses show that regulation based on the N-terminal region requires the presence of the inactive C-terminal helicase cassette. Together, our results outline an intricate system of regulatory mechanisms, which control Brr2 activities during snRNP assembly and splicing.

Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA helicase Brr2.,Absmeier E, Becke C, Wollenhaupt J, Santos KF, Wahl MC Cell Cycle. 2016 Nov 23:0. PMID:27880071^[9]

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

References

↑ Maeder C, Kutach AK, Guthrie C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nat Struct Mol Biol. 2009 Jan;16(1):42-8. doi: 10.1038/nsmb.1535. Epub 2008 Dec, 21. PMID:19098916 doi:http://dx.doi.org/10.1038/nsmb.1535
↑ Hahn D, Kudla G, Tollervey D, Beggs JD. Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning. Genes Dev. 2012 Nov 1;26(21):2408-21. doi: 10.1101/gad.199307.112. PMID:23124065 doi:http://dx.doi.org/10.1101/gad.199307.112
↑ Pena V, Jovin SM, Fabrizio P, Orlowski J, Bujnicki JM, Luhrmann R, Wahl MC. Common design principles in the spliceosomal RNA helicase Brr2 and in the Hel308 DNA helicase. Mol Cell. 2009 Aug 28;35(4):454-66. PMID:19716790 doi:10.1016/j.molcel.2009.08.006
↑ Zhang L, Xu T, Maeder C, Bud LO, Shanks J, Nix J, Guthrie C, Pleiss JA, Zhao R. Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol. 2009 Jul;16(7):731-9. Epub 2009 Jun 14. PMID:19525970 doi:10.1038/nsmb.1625
↑ Jackson SP, Lossky M, Beggs JD. Cloning of the RNA8 gene of Saccharomyces cerevisiae, detection of the RNA8 protein, and demonstration that it is essential for nuclear pre-mRNA splicing. Mol Cell Biol. 1988 Mar;8(3):1067-75. PMID:2835658
↑ Abovich N, Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997 May 2;89(3):403-12. PMID:9150140
↑ McPheeters DS, Muhlenkamp P. Spatial organization of protein-RNA interactions in the branch site-3' splice site region during pre-mRNA splicing in yeast. Mol Cell Biol. 2003 Jun;23(12):4174-86. PMID:12773561
↑ Yang K, Zhang L, Xu T, Heroux A, Zhao R. Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13817-22. Epub 2008 Sep 8. PMID:18779563
↑ Absmeier E, Becke C, Wollenhaupt J, Santos KF, Wahl MC. Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA helicase Brr2. Cell Cycle. 2016 Nov 23:0. PMID:27880071 doi:http://dx.doi.org/10.1080/15384101.2016.1255384

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5m5p"

@@ Line 1: / Line 1: @@
 ==S. cerevisiae spliceosomal helicase Brr2 (271-end) in complex with the Jab/MPN domain of S. cerevisiae Prp8==
-<StructureSection load='5m5p' size='340' side='right' caption='[[5m5p]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
+<StructureSection load='5m5p' size='340' side='right'caption='[[5m5p]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5m5p]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M5P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M5P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5m5p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M5P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M5P 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">BRR2, RSS1, SNU246, YER172C, SYGP-ORF66 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), PRP8, DBF3, DNA39, RNA8, SLT21, USA2, YHR165C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=5m5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m5p OCA], [http://pdbe.org/5m5p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m5p RCSB], [http://www.ebi.ac.uk/pdbsum/5m5p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m5p ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5m5p" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Helicase 3D structures|Helicase 3D structures]]
+*[[Pre-mRNA-splicing factor|Pre-mRNA-splicing factor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Baker's yeast]]
+[[Category: Large Structures]]
 [[Category: RNA helicase]]
 [[Category: Absmeier, E]]

5m5p

From Proteopedia

Revision as of 06:34, 16 October 2019

S. cerevisiae spliceosomal helicase Brr2 (271-end) in complex with the Jab/MPN domain of S. cerevisiae Prp8

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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