5dca: Difference between revisions

Line 1:

'''~~Unreleased~~ structure'''

==Crystal structure of yeast full length Brr2 in complex with Prp8 Jab1 domain==

== Structural highlights ==

<table><tr><td colspan='2'>[[5dca]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DCA 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>

<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=5dca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dca OCA], [http://pdbe.org/5dca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dca RCSB], [http://www.ebi.ac.uk/pdbsum/5dca PDBsum]</span></td></tr>

</table>

== Function ==

[[http://www.uniprot.org/uniprot/BRR2_YEAST 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.<ref>PMID:19098916</ref> <ref>PMID:23124065</ref> <ref>PMID:19716790</ref> <ref>PMID:19525970</ref> [[http://www.uniprot.org/uniprot/PRP8_YEAST 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.<ref>PMID:2835658</ref> <ref>PMID:9150140</ref> <ref>PMID:12773561</ref> <ref>PMID:18779563</ref>

== Publication Abstract from PubMed ==

The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an approximately 500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6*U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation.

The ~~entry 5dca is ON HOLD until Paper Publication~~

The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation.,Absmeier E, Wollenhaupt J, Mozaffari-Jovin S, Becke C, Lee CT, Preussner M, Heyd F, Urlaub H, Luhrmann R, Santos KF, Wahl MC Genes Dev. 2015 Dec 4. PMID:26637280<ref>PMID:26637280</ref>

~~Authors~~: Absmeier, E~~., Wollenhaupt, J.,~~ Santos, K.F~~., Wahl, M.C.~~

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

</div>

~~Description:~~

[[Category: ~~Unreleased Structures~~]]

== References ==

__TOC__

</StructureSection>

[[Category: RNA helicase]]

[[Category: Absmeier, E]]

[[Category: Santos, K F]]

[[Category: Wahl, M C]]

[[Category: Wollenhaupt, J]]

[[Category: ~~Wahl, M.C~~]]

[[Category: Helicase]]

[[Category: ~~Absmeier, E~~]]

[[Category: Hydrolase]]

[[Category: ~~Santos, K.F~~]]

[[Category: Protein complex]]

[[Category: Rnp remodeling]]

[[Category: Spliceosome activation]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of yeast full length Brr2 in complex with Prp8 Jab1 domain==
+<StructureSection load='5dca' size='340' side='right' caption='[[5dca]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5dca]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DCA 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>
+<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=5dca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dca OCA], [http://pdbe.org/5dca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dca RCSB], [http://www.ebi.ac.uk/pdbsum/5dca PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/BRR2_YEAST 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.<ref>PMID:19098916</ref> <ref>PMID:23124065</ref> <ref>PMID:19716790</ref> <ref>PMID:19525970</ref>  [[http://www.uniprot.org/uniprot/PRP8_YEAST 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.<ref>PMID:2835658</ref> <ref>PMID:9150140</ref> <ref>PMID:12773561</ref> <ref>PMID:18779563</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an approximately 500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6*U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation.
-The entry 5dca is ON HOLD  until Paper Publication
+The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation.,Absmeier E, Wollenhaupt J, Mozaffari-Jovin S, Becke C, Lee CT, Preussner M, Heyd F, Urlaub H, Luhrmann R, Santos KF, Wahl MC Genes Dev. 2015 Dec 4. PMID:26637280<ref>PMID:26637280</ref>
-Authors: Absmeier, E., Wollenhaupt, J., Santos, K.F., Wahl, M.C.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+<div class="pdbe-citations 5dca" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: RNA helicase]]
+[[Category: Absmeier, E]]
+[[Category: Santos, K F]]
+[[Category: Wahl, M C]]
 [[Category: Wollenhaupt, J]]
-[[Category: Wahl, M.C]]
+[[Category: Helicase]]
-[[Category: Absmeier, E]]
+[[Category: Hydrolase]]
-[[Category: Santos, K.F]]
+[[Category: Protein complex]]
+[[Category: Rnp remodeling]]
+[[Category: Spliceosome activation]]