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4c9b

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Revision as of 07:31, 4 August 2016

Crystal structure of eIF4AIII-CWC22 complex

Structural highlights

4c9b is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	RNA helicase, with EC number 3.6.4.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IF4A3_HUMAN] ATP-dependent RNA helicase. Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Constitutes at least part of the platform anchoring other EJC proteins to spliced mRNAs. Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH/RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH/RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed.^[1] ^[2] ^[3] ^[4] ^[5] [CWC22_HUMAN] Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.^[6] ^[7] ^[8]

Publication Abstract from PubMed

DEAD-box proteins are involved in all aspects of RNA processing. They bind RNA in an ATP-dependent manner and couple ATP hydrolysis to structural and compositional rearrangements of ribonucleoprotein particles. Conformational control is a major point of regulation for DEAD-box proteins to act on appropriate substrates and in a timely manner in vivo. Binding partners containing a middle domain of translation initiation factor 4G (MIF4G) are emerging as important regulators. Well-known examples are eIF4G and Gle1, which bind and activate the DEAD-box proteins eIF4A and Dbp5. Here, we report the mechanism of an inhibiting MIF4G domain. We determined the 2.0-A resolution structure of the complex of human eIF4AIII and the MIF4G domain of the splicing factor Complexed With Cef1 (CWC22), an essential prerequisite for exon junction complex assembly by the splicing machinery. The CWC22 MIF4G domain binds both RecA domains of eIF4AIII. The mode of RecA2 recognition is similar to that observed in the activating complexes, yet is specific for eIF4AIII. The way the CWC22 MIF4G domain latches on the eIF4AIII RecA1 domain is markedly different from activating complexes. In the CWC22-eIF4AIII complex, the RNA-binding and ATP-binding motifs of the two RecA domains do not face each other, as would be required in the active state, but are in diametrically opposite positions. The binding mode of CWC22 to eIF4AIII reveals a facet of how MIF4G domains use their versatile structural frameworks to activate or inhibit DEAD-box proteins.

Crystal structure of the human eIF4AIII-CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain.,Buchwald G, Schussler S, Basquin C, Le Hir H, Conti E Proc Natl Acad Sci U S A. 2013 Nov 11. PMID:24218557^[9]

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

References

↑ Shibuya T, Tange TO, Sonenberg N, Moore MJ. eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat Struct Mol Biol. 2004 Apr;11(4):346-51. Epub 2004 Mar 21. PMID:15034551 doi:http://dx.doi.org/10.1038/nsmb750
↑ Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75. PMID:16209946 doi:http://dx.doi.org/S1097-2765(05)01554-6
↑ Ballut L, Marchadier B, Baguet A, Tomasetto C, Seraphin B, Le Hir H. The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol. 2005 Oct;12(10):861-9. Epub 2005 Sep 18. PMID:16170325 doi:http://dx.doi.org/nsmb990
↑ Noble CG, Song H. MLN51 stimulates the RNA-helicase activity of eIF4AIII. PLoS One. 2007 Mar 21;2(3):e303. PMID:17375189 doi:http://dx.doi.org/10.1371/journal.pone.0000303
↑ Lee HC, Choe J, Chi SG, Kim YK. Exon junction complex enhances translation of spliced mRNAs at multiple steps. Biochem Biophys Res Commun. 2009 Jul 3;384(3):334-40. doi:, 10.1016/j.bbrc.2009.04.123. Epub 2009 May 3. PMID:19409878 doi:http://dx.doi.org/10.1016/j.bbrc.2009.04.123
↑ Steckelberg AL, Boehm V, Gromadzka AM, Gehring NH. CWC22 connects pre-mRNA splicing and exon junction complex assembly. Cell Rep. 2012 Sep 27;2(3):454-61. doi: 10.1016/j.celrep.2012.08.017. Epub 2012, Sep 6. PMID:22959432 doi:http://dx.doi.org/10.1016/j.celrep.2012.08.017
↑ Barbosa I, Haque N, Fiorini F, Barrandon C, Tomasetto C, Blanchette M, Le Hir H. Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. Nat Struct Mol Biol. 2012 Oct;19(10):983-90. doi: 10.1038/nsmb.2380. Epub 2012, Sep 9. PMID:22961380 doi:http://dx.doi.org/10.1038/nsmb.2380
↑ Alexandrov A, Colognori D, Shu MD, Steitz JA. Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21313-8. doi:, 10.1073/pnas.1219725110. Epub 2012 Dec 10. PMID:23236153 doi:http://dx.doi.org/10.1073/pnas.1219725110
↑ Buchwald G, Schussler S, Basquin C, Le Hir H, Conti E. Crystal structure of the human eIF4AIII-CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain. Proc Natl Acad Sci U S A. 2013 Nov 11. PMID:24218557 doi:http://dx.doi.org/10.1073/pnas.1314684110

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/4c9b"

@@ Line 1: / Line 1: @@
 ==Crystal structure of eIF4AIII-CWC22 complex==
 <StructureSection load='4c9b' size='340' side='right' caption='[[4c9b]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4c9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c9b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c9b RCSB], [http://www.ebi.ac.uk/pdbsum/4c9b PDBsum]</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=4c9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c9b OCA], [http://pdbe.org/4c9b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c9b RCSB], [http://www.ebi.ac.uk/pdbsum/4c9b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c9b ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4c9b" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Eukaryotic initiation factor|Eukaryotic initiation factor]]
 == References ==
 <references/>

4c9b

From Proteopedia

Revision as of 07:31, 4 August 2016

Crystal structure of eIF4AIII-CWC22 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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