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5t46

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Revision as of 11:20, 16 September 2020

Crystal structure of the human eIF4E-eIF4G complex

Structural highlights

5t46 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:	,
Gene:	EIF4E, EIF4EL1, EIF4F (HUMAN), EIF4G1, EIF4F, EIF4G, EIF4GI (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IF4G1_HUMAN] Defects in EIF4G1 are the cause of Parkinson disease type 18 (PARK18) [MIM:614251]. An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.^[1]

Function

[IF4E_HUMAN] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). 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. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.^[2] [IF4G1_HUMAN] Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.

Publication Abstract from PubMed

Eukaryotic initiation factor 4G (eIF4G) plays a central role in translation initiation through its interactions with the cap-binding protein eIF4E. This interaction is a major drug target for repressing translation and is naturally regulated by 4E-binding proteins (4E-BPs). 4E-BPs and eIF4G compete for binding to the eIF4E dorsal surface via a shared canonical 4E-binding motif, but also contain auxiliary eIF4E-binding sequences, which were assumed to contact non-overlapping eIF4E surfaces. However, it is unknown how metazoan eIF4G auxiliary sequences bind eIF4E. Here, we describe crystal structures of human and Drosophila melanogaster eIF4E-eIF4G complexes, which unexpectedly reveal that the eIF4G auxiliary sequences bind to the lateral surface of eIF4E, using a similar mode to that of 4E-BPs. Our studies provide a molecular model of the eIF4E-eIF4G complex, shed light on the competition mechanism of 4E-BPs, and enable the rational design of selective eIF4G inhibitors to dampen dysregulated translation in disease.

The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation.,Gruner S, Peter D, Weber R, Wohlbold L, Chung MY, Weichenrieder O, Valkov E, Igreja C, Izaurralde E Mol Cell. 2016 Oct 19. pii: S1097-2765(16)30569-X. doi:, 10.1016/j.molcel.2016.09.020. PMID:27773676^[3]

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

References

↑ Chartier-Harlin MC, Dachsel JC, Vilarino-Guell C, Lincoln SJ, Lepretre F, Hulihan MM, Kachergus J, Milnerwood AJ, Tapia L, Song MS, Le Rhun E, Mutez E, Larvor L, Duflot A, Vanbesien-Mailliot C, Kreisler A, Ross OA, Nishioka K, Soto-Ortolaza AI, Cobb SA, Melrose HL, Behrouz B, Keeling BH, Bacon JA, Hentati E, Williams L, Yanagiya A, Sonenberg N, Lockhart PJ, Zubair AC, Uitti RJ, Aasly JO, Krygowska-Wajs A, Opala G, Wszolek ZK, Frigerio R, Maraganore DM, Gosal D, Lynch T, Hutchinson M, Bentivoglio AR, Valente EM, Nichols WC, Pankratz N, Foroud T, Gibson RA, Hentati F, Dickson DW, Destee A, Farrer MJ. Translation initiator EIF4G1 mutations in familial Parkinson disease. Am J Hum Genet. 2011 Sep 9;89(3):398-406. doi: 10.1016/j.ajhg.2011.08.009. PMID:21907011 doi:10.1016/j.ajhg.2011.08.009
↑ Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, Miyagawa H, Kitamura K, Miura K, Ishida T. Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. Biochim Biophys Acta. 2005 Dec 1;1753(2):191-208. Epub 2005 Aug 24. PMID:16271312 doi:10.1016/j.bbapap.2005.07.023
↑ Gruner S, Peter D, Weber R, Wohlbold L, Chung MY, Weichenrieder O, Valkov E, Igreja C, Izaurralde E. The Structures of eIF4E-eIF4G Complexes Reveal an Extended Interface to Regulate Translation Initiation. Mol Cell. 2016 Oct 19. pii: S1097-2765(16)30569-X. doi:, 10.1016/j.molcel.2016.09.020. PMID:27773676 doi:http://dx.doi.org/10.1016/j.molcel.2016.09.020

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5t46"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human eIF4E-eIF4G complex==
-<StructureSection load='5t46' size='340' side='right' caption='[[5t46]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
+<StructureSection load='5t46' size='340' side='right'caption='[[5t46]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5t46]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T46 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T46 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5t46]] 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=5T46 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T46 FirstGlance]. <br>
-</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=MGP:7-METHYL-GUANOSINE-5-TRIPHOSPHATE'>MGP</scene></td></tr>
+</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=MGP:7-METHYL-GUANOSINE-5-TRIPHOSPHATE'>MGP</scene></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=5t46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t46 OCA], [http://pdbe.org/5t46 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t46 RCSB], [http://www.ebi.ac.uk/pdbsum/5t46 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t46 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E, EIF4EL1, EIF4F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4G1, EIF4F, EIF4G, EIF4GI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5t46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t46 OCA], [http://pdbe.org/5t46 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t46 RCSB], [http://www.ebi.ac.uk/pdbsum/5t46 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t46 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5t46" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chung, M Y]]
 [[Category: Gruener, S]]

5t46

From Proteopedia

Revision as of 11:20, 16 September 2020

Crystal structure of the human eIF4E-eIF4G complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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