4c9b

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:10, 9 May 2024) (edit) (undo)
 
(4 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_4c9b| PDB=4c9b | SCENE= }}
 
-
===Crystal structure of eIF4AIII-CWC22 complex===
 
-
{{ABSTRACT_PUBMED_24218557}}
 
-
==Function==
+
==Crystal structure of eIF4AIII-CWC22 complex==
-
[[http://www.uniprot.org/uniprot/IF4A3_HUMAN 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.<ref>PMID:15034551</ref> <ref>PMID:16209946</ref> <ref>PMID:16170325</ref> <ref>PMID:17375189</ref> <ref>PMID:19409878</ref> [[http://www.uniprot.org/uniprot/CWC22_HUMAN 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.<ref>PMID:22959432</ref> <ref>PMID:22961380</ref> <ref>PMID:23236153</ref>
+
<StructureSection load='4c9b' size='340' side='right'caption='[[4c9b]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4c9b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C9B 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&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4c9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c9b OCA], [https://pdbe.org/4c9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c9b RCSB], [https://www.ebi.ac.uk/pdbsum/4c9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c9b ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/IF4A3_HUMAN 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.<ref>PMID:15034551</ref> <ref>PMID:16209946</ref> <ref>PMID:16170325</ref> <ref>PMID:17375189</ref> <ref>PMID:19409878</ref>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
==About this Structure==
+
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<ref>PMID:24218557</ref>
-
[[4c9b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C9B OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<ref group="xtra">PMID:024218557</ref><references group="xtra"/><references/>
+
</div>
-
[[Category: Human]]
+
<div class="pdbe-citations 4c9b" style="background-color:#fffaf0;"></div>
-
[[Category: RNA helicase]]
+
 
-
[[Category: Basquin, C.]]
+
==See Also==
-
[[Category: Buchwald, G.]]
+
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
-
[[Category: Conti, E.]]
+
*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]]
-
[[Category: LeHir, H.]]
+
== References ==
-
[[Category: Schuessler, S.]]
+
<references/>
-
[[Category: Dead-box helicase]]
+
__TOC__
-
[[Category: Mrnp]]
+
</StructureSection>
-
[[Category: Nmd]]
+
[[Category: Homo sapiens]]
-
[[Category: Splicing]]
+
[[Category: Large Structures]]
 +
[[Category: Basquin C]]
 +
[[Category: Buchwald G]]
 +
[[Category: Conti E]]
 +
[[Category: LeHir H]]
 +
[[Category: Schuessler S]]

Current revision

Crystal structure of eIF4AIII-CWC22 complex

PDB ID 4c9b

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4c9b"
Personal tools