6hyt: Difference between revisions
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==Crystal structure of DHX8 helicase domain bound to ADP at 2.3 Angstrom== | |||
<StructureSection load='6hyt' size='340' side='right'caption='[[6hyt]], [[Resolution|resolution]] 2.33Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6hyt]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HYT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HYT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6hyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hyt OCA], [http://pdbe.org/6hyt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hyt RCSB], [http://www.ebi.ac.uk/pdbsum/6hyt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hyt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/DHX8_HUMAN DHX8_HUMAN]] Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.<ref>PMID:8608946</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here we report the biochemical characterization of full-length human DHX8 and the catalytically active helicase core DHX8Delta547, alongside crystal structures of DHX8Delta547 bound to ADP and a structure of DHX8Delta547 bound to poly(A)6 single-strand RNA. Our results reveal that DHX8 has an in vitro binding preference for adenine-rich RNA and that RNA binding triggers release of ADP through significant conformational flexibility in the conserved DEAH-, P-loop and hook-turn motifs. We demonstrate the importance of R620 and both the hook-turn and hook-loop regions for DHX8 helicase activity, and propose that the hook-turn acts as a gatekeeper to regulate directional movement of the 3' end of RNA through the RNA binding channel. This study provides an in-depth understanding of the activity of DHX8 and contributes insights into the RNA unwinding mechanisms of the DEAH-box helicase family. | |||
Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release.,Felisberto-Rodrigues C, Thomas JC, McAndrew C, Le Bihan YV, Burke R, Workman P, van Montfort RLM Biochem J. 2019 Aug 13. pii: BCJ20190383. doi: 10.1042/BCJ20190383. PMID:31409651<ref>PMID:31409651</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6hyt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: RNA helicase]] | |||
[[Category: Bihan, Y V.Le]] | |||
[[Category: Burke, R]] | [[Category: Burke, R]] | ||
[[Category: Felisberto-Rodrigues, C]] | [[Category: Felisberto-Rodrigues, C]] | ||
[[Category: | [[Category: McAndrew, P C]] | ||
[[Category: Montfort, R L.M van]] | |||
[[Category: Thomas, J C]] | |||
[[Category: Workman, P]] | [[Category: Workman, P]] | ||
[[Category: | [[Category: Helicase]] | ||
[[Category: | [[Category: Rna]] | ||
[[Category: | [[Category: Rna binding protein]] | ||
[[Category: Splicing]] | |||
Latest revision as of 18:25, 28 August 2019
Crystal structure of DHX8 helicase domain bound to ADP at 2.3 AngstromCrystal structure of DHX8 helicase domain bound to ADP at 2.3 Angstrom
Structural highlights
Function[DHX8_HUMAN] Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.[1] Publication Abstract from PubMedDHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here we report the biochemical characterization of full-length human DHX8 and the catalytically active helicase core DHX8Delta547, alongside crystal structures of DHX8Delta547 bound to ADP and a structure of DHX8Delta547 bound to poly(A)6 single-strand RNA. Our results reveal that DHX8 has an in vitro binding preference for adenine-rich RNA and that RNA binding triggers release of ADP through significant conformational flexibility in the conserved DEAH-, P-loop and hook-turn motifs. We demonstrate the importance of R620 and both the hook-turn and hook-loop regions for DHX8 helicase activity, and propose that the hook-turn acts as a gatekeeper to regulate directional movement of the 3' end of RNA through the RNA binding channel. This study provides an in-depth understanding of the activity of DHX8 and contributes insights into the RNA unwinding mechanisms of the DEAH-box helicase family. Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release.,Felisberto-Rodrigues C, Thomas JC, McAndrew C, Le Bihan YV, Burke R, Workman P, van Montfort RLM Biochem J. 2019 Aug 13. pii: BCJ20190383. doi: 10.1042/BCJ20190383. PMID:31409651[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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