View source for 5dca


==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 with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5DCA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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=5dca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dca OCA], [https://pdbe.org/5dca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dca RCSB], [https://www.ebi.ac.uk/pdbsum/5dca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dca ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
<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 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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5dca" 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/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Absmeier E]]
[[Category: Santos KF]]
[[Category: Wahl MC]]
[[Category: Wollenhaupt J]]