View source for 2mx4


==NMR structure of Phosphorylated 4E-BP2==
<StructureSection load='2mx4' size='340' side='right'caption='[[2mx4]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mx4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MX4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=2mx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mx4 OCA], [https://pdbe.org/2mx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mx4 RCSB], [https://www.ebi.ac.uk/pdbsum/2mx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mx4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/4EBP2_HUMAN 4EBP2_HUMAN] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase pathway.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Intrinsically disordered proteins play important roles in cell signalling, transcription, translation and cell cycle regulation. Although they lack stable tertiary structure, many intrinsically disordered proteins undergo disorder-to-order transitions upon binding to partners. Similarly, several folded proteins use regulated order-to-disorder transitions to mediate biological function. In principle, the function of intrinsically disordered proteins may be controlled by post-translational modifications that lead to structural changes such as folding, although this has not been observed. Here we show that multisite phosphorylation induces folding of the intrinsically disordered 4E-BP2, the major neural isoform of the family of three mammalian proteins that bind eIF4E and suppress cap-dependent translation initiation. In its non-phosphorylated state, 4E-BP2 interacts tightly with eIF4E using both a canonical YXXXXLPhi motif (starting at Y54) that undergoes a disorder-to-helix transition upon binding and a dynamic secondary binding site. We demonstrate that phosphorylation at T37 and T46 induces folding of residues P18-R62 of 4E-BP2 into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking its accessibility to eIF4E. The folded state of pT37pT46 4E-BP2 is weakly stable, decreasing affinity by 100-fold and leading to an order-to-disorder transition upon binding to eIF4E, whereas fully phosphorylated 4E-BP2 is more stable, decreasing affinity by a factor of approximately 4,000. These results highlight stabilization of a phosphorylation-induced fold as the essential mechanism for phospho-regulation of the 4E-BP:eIF4E interaction and exemplify a new mode of biological regulation mediated by intrinsically disordered proteins.

Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch.,Bah A, Vernon RM, Siddiqui Z, Krzeminski M, Muhandiram R, Zhao C, Sonenberg N, Kay LE, Forman-Kay JD Nature. 2014 Dec 22. doi: 10.1038/nature13999. PMID:25533957<ref>PMID:25533957</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mx4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bah A]]
[[Category: Forman-Kay J]]
[[Category: Kay L]]
[[Category: Krzeminski M]]
[[Category: Muhandiram R]]
[[Category: Siddiqui Z]]
[[Category: Sonenberg N]]
[[Category: Vernon R]]
[[Category: Zhao C]]