6s8s: Difference between revisions

Revision as of 06:26, 10 October 2019

Extended structure of the human DDX6 C-terminal domain in complex with an EDC3 FDF peptide

Structural highlights

6s8s is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CXS, PO4
Related:	2wax
Gene:	DDX6, HLR2, RCK (HUMAN), EDC3, LSM16, YJDC, YJEFN2, PP844 (HUMAN)
Activity:	RNA helicase, with EC number 3.6.4.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[DDX6_HUMAN] Note=A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).

Function

[DDX6_HUMAN] In the process of mRNA degradation, may play a role in mRNA decapping. [EDC3_HUMAN] Binds single-stranded RNA. In the process of mRNA degradation, may play a role in mRNA decapping. May play a role in spermiogenesis and oogenesis.^[1] ^[2] ^[3]

Publication Abstract from PubMed

GIGYF (Grb10-interacting GYF [glycine-tyrosine-phenylalanine domain]) proteins coordinate with 4EHP (eIF4E [eukaryotic initiation factor 4E] homologous protein), the DEAD (Asp-Glu-Ala-Asp)-box helicase Me31B/DDX6, and mRNA-binding proteins to elicit transcript-specific repression. However, the underlying molecular mechanism remains unclear. Here, we report that GIGYF contains a motif necessary and sufficient for direct interaction with Me31B/DDX6. A 2.4 A crystal structure of the GIGYF-Me31B complex reveals that this motif arranges into a coil connected to a beta hairpin on binding to conserved hydrophobic patches on the Me31B RecA2 domain. Structure-guided mutants indicate that 4EHP-GIGYF-DDX6 complex assembly is required for tristetraprolin-mediated down-regulation of an AU-rich mRNA, thus revealing the molecular principles of translational repression.

Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression.,Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E Genes Dev. 2019 Oct 1;33(19-20):1355-1360. doi: 10.1101/gad.329219.119. Epub 2019, Aug 22. PMID:31439631^[4]

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

References

↑ Fenger-Gron M, Fillman C, Norrild B, Lykke-Andersen J. Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping. Mol Cell. 2005 Dec 22;20(6):905-15. PMID:16364915 doi:S1097-2765(05)01726-0
↑ Rudolph C, Sigruener A, Hartmann A, Orso E, Bals-Pratsch M, Gronwald W, Seifert B, Kalbitzer HR, Verdorfer I, Luetjens CM, Ortmann O, Bornstein SR, Schmitz G. ApoA-I-binding protein (AI-BP) and its homologues hYjeF_N2 and hYjeF_N3 comprise the YjeF_N domain protein family in humans with a role in spermiogenesis and oogenesis. Horm Metab Res. 2007 May;39(5):322-35. PMID:17533573 doi:10.1055/s-2007-977699
↑ Ling SH, Decker CJ, Walsh MA, She M, Parker R, Song H. Crystal structure of human Edc3 and its functional implications. Mol Cell Biol. 2008 Oct;28(19):5965-76. Epub 2008 Aug 4. PMID:18678652 doi:10.1128/MCB.00761-08
↑ Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E. Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression. Genes Dev. 2019 Oct 1;33(19-20):1355-1360. doi: 10.1101/gad.329219.119. Epub 2019, Aug 22. PMID:31439631 doi:https://dx.doi.org/10.1101/gad.329219.119

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Fenger-Gron M, Fillman C, Norrild B, Lykke-Andersen J. Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping. Mol Cell. 2005 Dec 22;20(6):905-15. PMID:16364915 doi:S1097-2765(05)01726-0

[2] Rudolph C, Sigruener A, Hartmann A, Orso E, Bals-Pratsch M, Gronwald W, Seifert B, Kalbitzer HR, Verdorfer I, Luetjens CM, Ortmann O, Bornstein SR, Schmitz G. ApoA-I-binding protein (AI-BP) and its homologues hYjeF_N2 and hYjeF_N3 comprise the YjeF_N domain protein family in humans with a role in spermiogenesis and oogenesis. Horm Metab Res. 2007 May;39(5):322-35. PMID:17533573 doi:10.1055/s-2007-977699

[3] Ling SH, Decker CJ, Walsh MA, She M, Parker R, Song H. Crystal structure of human Edc3 and its functional implications. Mol Cell Biol. 2008 Oct;28(19):5965-76. Epub 2008 Aug 4. PMID:18678652 doi:10.1128/MCB.00761-08

[4] Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E. Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression. Genes Dev. 2019 Oct 1;33(19-20):1355-1360. doi: 10.1101/gad.329219.119. Epub 2019, Aug 22. PMID:31439631 doi:https://dx.doi.org/10.1101/gad.329219.119

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6s8s is ON HOLD  until Paper Publication
+==Extended structure of the human DDX6 C-terminal domain in complex with an EDC3 FDF peptide==
+<StructureSection load='6s8s' size='340' side='right'caption='[[6s8s]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6s8s]] is a 4 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=6S8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S8S FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wax|2wax]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDX6, HLR2, RCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EDC3, LSM16, YJDC, YJEFN2, PP844 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6s8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s8s OCA], [http://pdbe.org/6s8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s8s RCSB], [http://www.ebi.ac.uk/pdbsum/6s8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s8s ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/DDX6_HUMAN DDX6_HUMAN]] Note=A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
+== Function ==
+[[http://www.uniprot.org/uniprot/DDX6_HUMAN DDX6_HUMAN]] In the process of mRNA degradation, may play a role in mRNA decapping. [[http://www.uniprot.org/uniprot/EDC3_HUMAN EDC3_HUMAN]] Binds single-stranded RNA. In the process of mRNA degradation, may play a role in mRNA decapping. May play a role in spermiogenesis and oogenesis.<ref>PMID:16364915</ref> <ref>PMID:17533573</ref> <ref>PMID:18678652</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+GIGYF (Grb10-interacting GYF [glycine-tyrosine-phenylalanine domain]) proteins coordinate with 4EHP (eIF4E [eukaryotic initiation factor 4E] homologous protein), the DEAD (Asp-Glu-Ala-Asp)-box helicase Me31B/DDX6, and mRNA-binding proteins to elicit transcript-specific repression. However, the underlying molecular mechanism remains unclear. Here, we report that GIGYF contains a motif necessary and sufficient for direct interaction with Me31B/DDX6. A 2.4 A crystal structure of the GIGYF-Me31B complex reveals that this motif arranges into a coil connected to a beta hairpin on binding to conserved hydrophobic patches on the Me31B RecA2 domain. Structure-guided mutants indicate that 4EHP-GIGYF-DDX6 complex assembly is required for tristetraprolin-mediated down-regulation of an AU-rich mRNA, thus revealing the molecular principles of translational repression.
-Authors:
+Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression.,Peter D, Ruscica V, Bawankar P, Weber R, Helms S, Valkov E, Igreja C, Izaurralde E Genes Dev. 2019 Oct 1;33(19-20):1355-1360. doi: 10.1101/gad.329219.119. Epub 2019, Aug 22. PMID:31439631<ref>PMID:31439631</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6s8s" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: RNA helicase]]
+[[Category: Peter, D]]
+[[Category: Valkov, E]]
+[[Category: Mirna]]
+[[Category: Mrna decay]]
+[[Category: Rna binding protein]]
+[[Category: Translational control]]

6s8s: Difference between revisions

Revision as of 06:26, 10 October 2019

Extended structure of the human DDX6 C-terminal domain in complex with an EDC3 FDF peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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