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New page: left|200px<br /> <applet load="1wkw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wkw, resolution 2.1Å" /> '''Crystal structure of...
 
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[[Image:1wkw.gif|left|200px]]<br />
<applet load="1wkw" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1wkw, resolution 2.1&Aring;" />
'''Crystal structure of the ternary complex of eIF4E-m7GpppA-4EBP1 peptide'''<br />


==Overview==
==Crystal structure of the ternary complex of eIF4E-m7GpppA-4EBP1 peptide==
Taking advantage of the Trp73 residue located close to the 4E-BP binding, site of eIF4E, the interaction between the 4E-BP isoform and eIF4E was, investigated by the Trp fluorescence titration method. Although no, significant difference was observed among the association constants of, three 4E-BP isoforms, the binding preference of 4E-BP2 over 4E-BP1 and, -BP3 was shown, probably due to the effect of a 4E-BP2-specific LDRR, (60-63) sequence for the binding with eIF4E. By contrast, surface plasmon, resonance (SPR) analyses showed the binding preference of 4E-BP1, although, the difference among the isoforms was also not significant. This, inconsistency with fluorescence analysis likely resulted from the, different observation points of the interaction, i.e., local and overall, interactions observed by the fluorescence and SPR methods, respectively., To clarify the structural basis for these spectroscopic results, the, crystal structure of the ternary complex of m7GpppA-eIF4E-4E-BP1 fragment, (Thr36-Thr70) was analyzed by the X-ray diffraction method. Crystal, structure analysis at 2.1 A resolution revealed that the 4E-BP1 fragment, assigned to the Pro47-Pro66 peptide moiety, adopted a reverse L-shaped, conformation involving the beta sheet and alpha-helical structures and was, located at the root of the handle of the temple-bell-shaped eIF4E through, hydrophilic and hydrophobic interactions. Based on the observed binding, mode, possible interactions with the three 4E-BP isoforms have been, discussed. On the other hand, since the crystal structural comparison with, the previously determined m7GpppA-eIF4E-4E binary complex showed that the, docking of the 4E-BP1 fragment does not significantly affect the overall, tertiary structure and cap-binding scaffold of eIF4E, the dynamic, regulation of the cap-binding of eIF4E by 4E-BP1 was investigated by, molecular dynamics (MD) simulations. Consequently, the simulation, suggested that (i) the helical region of the 4E-BP1 peptide is important, for the binding with eIF4E, (ii) the existence of a cap structure, stabilizes the binding of eIF4E with 4E-BP, (iii) the binding of 4E-BP, stabilizes the cap-binding pocket of eIF4E, and (iv) the phosphorylation, of Ser67 alone does not induce the separation of 4E-BP from eIF4E, but, increases the structural rigidity of 4E-BP. These results provide the, structural basis for the mRNA cap-binding regulation of eIF4E by 4E-BP.
<StructureSection load='1wkw' size='340' side='right'caption='[[1wkw]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wkw]] 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=1WKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WKW 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTA:P1-7-METHYLGUANOSINE-P3-ADENOSINE-5,5-TRIPHOSPHATE'>GTA</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=1wkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wkw OCA], [https://pdbe.org/1wkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wkw RCSB], [https://www.ebi.ac.uk/pdbsum/1wkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wkw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IF4E_HUMAN 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.<ref>PMID:16271312</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wk/1wkw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wkw ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1WKW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GTA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WKW OCA].
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
 
== References ==
==Reference==
<references/>
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., Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, Miyagawa H, Kitamura K, Miura K, Ishida T, Biochim Biophys Acta. 2005 Dec 1;1753(2):191-208. Epub 2005 Aug 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16271312 16271312]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Fujisaki, H.]]
[[Category: Fujisaki H]]
[[Category: Ishida, T.]]
[[Category: Ishida T]]
[[Category: Kitamura, K.]]
[[Category: Kitamura K]]
[[Category: Matsushita, Y.]]
[[Category: Matsushita Y]]
[[Category: Miura, K.]]
[[Category: Miura K]]
[[Category: Miyagawa, H.]]
[[Category: Miyagawa H]]
[[Category: Shen, X.]]
[[Category: Shen X]]
[[Category: Tomoo, K.]]
[[Category: Tomoo K]]
[[Category: GTA]]
[[Category: cap-binding protein]]
[[Category: initiation factor]]
[[Category: mrna-cap]]
[[Category: translation]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:52:03 2007''

Latest revision as of 13:31, 13 March 2024

Crystal structure of the ternary complex of eIF4E-m7GpppA-4EBP1 peptide

1wkw, resolution 2.10Å

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