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4axg

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Revision as of 12:34, 11 August 2016

Structure of eIF4E-Cup complex

Structural highlights

4axg is a 4 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IF4E_DROME] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures.^[1] [CUP_DROME] Adapter protein that plays a central role in localization of transcripts in the oocyte and in young embryos (PubMed:9118812). Maintains RNA targets in a repressed state by promoting their deadenylation and protects deadenylated mRNAs from further degradation (PubMed:21937713). Binds to and recruits eIF-4E to the 3'-UTR of some mRNA targets which prevents interaction between eIF-4E and eIF4G (PubMed:14685270, PubMed:15465908, PubMed:21081899). This may contribute to translational repression but does not appear to be necessary for it to occur. Can promote translational repression independently of deadenylation and eIF-4E binding (PubMed:21937713). Required for correct localization of eIF-4E in the developing oocyte (PubMed:15465908). Required for translational repression of oskar (osk) mRNA (PubMed:14691132, PubMed:14723848). Also required for the translational repression of nanos (nos) mRNA (PubMed:21081899). Promotes the accumulation of the germ plasm components osk, vas and stau at the posterior pole of the oocyte and is required for germ cell development (PubMed:22454519). Represses orb positive autoregulatory activity which prevents premature activation of orb and ensures its accumulation specifically in the developing oocyte (PubMed:22164257).^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Publication Abstract from PubMed

Cup is an eIF4E-binding protein (4E-BP) that plays a central role in translational regulation of localized mRNAs during early Drosophila development. In particular, Cup is required for repressing translation of the maternally contributed oskar, nanos, and gurken mRNAs, all of which are essential for embryonic body axis determination. Here, we present the 2.8 A resolution crystal structure of a minimal eIF4E-Cup assembly, consisting of the interacting regions of the two proteins. In the structure, two separate segments of Cup contact two orthogonal faces of eIF4E. The eIF4E-binding consensus motif of Cup (YXXXXLPhi) binds the convex side of eIF4E similarly to the consensus of other eIF4E-binding proteins, such as 4E-BPs and eIF4G. The second, noncanonical, eIF4E-binding site of Cup binds laterally and perpendicularly to the eIF4E beta-sheet. Mutations of Cup at this binding site were shown to reduce binding to eIF4E and to promote the destabilization of the associated mRNA. Comparison with the binding mode of eIF4G to eIF4E suggests that Cup and eIF4G binding would be mutually exclusive at both binding sites. This shows how a common molecular surface of eIF4E might recognize different proteins acting at different times in the same pathway. The structure provides insight into the mechanism by which Cup disrupts eIF4E-eIF4G interaction and has broader implications for understanding the role of 4E-BPs in translational regulation.

Crystal structure of a minimal eIF4E-Cup complex reveals a general mechanism of eIF4E regulation in translational repression.,Kinkelin K, Veith K, Grunwald M, Bono F RNA. 2012 Sep;18(9):1624-34. Epub 2012 Jul 25. PMID:22832024^[11]

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

References

↑ Lavoie CA, Lachance PE, Sonenberg N, Lasko P. Alternatively spliced transcripts from the Drosophila eIF4E gene produce two different Cap-binding proteins. J Biol Chem. 1996 Jul 5;271(27):16393-8. PMID:8663200
↑ Nelson MR, Leidal AM, Smibert CA. Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression. EMBO J. 2004 Jan 14;23(1):150-9. Epub 2003 Dec 11. PMID:14685270 doi:http://dx.doi.org/10.1038/sj.emboj.7600026
↑ Wilhelm JE, Hilton M, Amos Q, Henzel WJ. Cup is an eIF4E binding protein required for both the translational repression of oskar and the recruitment of Barentsz. J Cell Biol. 2003 Dec 22;163(6):1197-204. PMID:14691132 doi:http://dx.doi.org/10.1083/jcb.200309088
↑ Nakamura A, Sato K, Hanyu-Nakamura K. Drosophila cup is an eIF4E binding protein that associates with Bruno and regulates oskar mRNA translation in oogenesis. Dev Cell. 2004 Jan;6(1):69-78. PMID:14723848
↑ Jeske M, Moritz B, Anders A, Wahle E. Smaug assembles an ATP-dependent stable complex repressing nanos mRNA translation at multiple levels. EMBO J. 2011 Jan 5;30(1):90-103. doi: 10.1038/emboj.2010.283. Epub 2010 Nov 16. PMID:21081899 doi:http://dx.doi.org/10.1038/emboj.2010.283
↑ Igreja C, Izaurralde E. CUP promotes deadenylation and inhibits decapping of mRNA targets. Genes Dev. 2011 Sep 15;25(18):1955-67. doi: 10.1101/gad.17136311. PMID:21937713 doi:http://dx.doi.org/10.1101/gad.17136311
↑ Wong LC, Schedl P. Cup blocks the precocious activation of the orb autoregulatory loop. PLoS One. 2011;6(12):e28261. doi: 10.1371/journal.pone.0028261. Epub 2011 Dec 2. PMID:22164257 doi:http://dx.doi.org/10.1371/journal.pone.0028261
↑ Ottone C, Gigliotti S, Giangrande A, Graziani F, Verrotti di Pianella A. The translational repressor Cup is required for germ cell development in Drosophila. J Cell Sci. 2012 Jul 1;125(Pt 13):3114-23. doi: 10.1242/jcs.095208. Epub 2012 Mar, 27. PMID:22454519 doi:http://dx.doi.org/10.1242/jcs.095208
↑ Keyes LN, Spradling AC. The Drosophila gene fs(2)cup interacts with otu to define a cytoplasmic pathway required for the structure and function of germ-line chromosomes. Development. 1997 Apr;124(7):1419-31. PMID:9118812
↑ Igreja C, Izaurralde E. CUP promotes deadenylation and inhibits decapping of mRNA targets. Genes Dev. 2011 Sep 15;25(18):1955-67. doi: 10.1101/gad.17136311. PMID:21937713 doi:http://dx.doi.org/10.1101/gad.17136311
↑ Kinkelin K, Veith K, Grunwald M, Bono F. Crystal structure of a minimal eIF4E-Cup complex reveals a general mechanism of eIF4E regulation in translational repression. RNA. 2012 Sep;18(9):1624-34. Epub 2012 Jul 25. PMID:22832024 doi:10.1261/rna.033639.112

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/4axg"

@@ Line 1: / Line 1: @@
 ==Structure of eIF4E-Cup complex==
 <StructureSection load='4axg' size='340' side='right' caption='[[4axg]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4axg]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4axg]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXG FirstGlance]. <br>
-</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=4axg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4axg RCSB], [http://www.ebi.ac.uk/pdbsum/4axg PDBsum]</span></td></tr>
+</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=4axg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axg OCA], [http://pdbe.org/4axg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4axg RCSB], [http://www.ebi.ac.uk/pdbsum/4axg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4axg ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/IF4E_DROME IF4E_DROME]] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures.<ref>PMID:8663200</ref>  [[http://www.uniprot.org/uniprot/CUP_DROME CUP_DROME]] Adapter protein that plays a central role in localization of transcripts in the oocyte and in young embryos (PubMed:9118812). Maintains RNA targets in a repressed state by promoting their deadenylation and protects deadenylated mRNAs from further degradation (PubMed:21937713). Binds to and recruits eIF-4E to the 3'-UTR of some mRNA targets which prevents interaction between eIF-4E and eIF4G (PubMed:14685270, PubMed:15465908, PubMed:21081899). This may contribute to translational repression but does not appear to be necessary for it to occur. Can promote translational repression independently of deadenylation and eIF-4E binding (PubMed:21937713). Required for correct localization of eIF-4E in the developing oocyte (PubMed:15465908). Required for translational repression of oskar (osk) mRNA (PubMed:14691132, PubMed:14723848). Also required for the translational repression of nanos (nos) mRNA (PubMed:21081899). Promotes the accumulation of the germ plasm components osk, vas and stau at the posterior pole of the oocyte and is required for germ cell development (PubMed:22454519). Represses orb positive autoregulatory activity which prevents premature activation of orb and ensures its accumulation specifically in the developing oocyte (PubMed:22164257).<ref>PMID:14685270</ref> <ref>PMID:14691132</ref> <ref>PMID:14723848</ref> <ref>PMID:21081899</ref> <ref>PMID:21937713</ref> <ref>PMID:22164257</ref> <ref>PMID:22454519</ref> <ref>PMID:9118812</ref> <ref>PMID:21937713</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 13: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4axg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Eukaryotic initiation factor|Eukaryotic initiation factor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Drosophila melanogaster]]
+[[Category: Drome]]
 [[Category: Bono, F]]
 [[Category: Gruenwald, M]]

4axg

From Proteopedia

Revision as of 12:34, 11 August 2016

Structure of eIF4E-Cup complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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