6x2p: Difference between revisions
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==== | ==Crystal Structure of the Mek1NES peptide bound to CRM1== | ||
<StructureSection load='6x2p' size='340' side='right'caption='[[6x2p]]' scene=''> | <StructureSection load='6x2p' size='340' side='right'caption='[[6x2p]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6x2p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X2P FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.401Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6x2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x2p OCA], [https://pdbe.org/6x2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x2p RCSB], [https://www.ebi.ac.uk/pdbsum/6x2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x2p ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/XPO1_YEAST XPO1_YEAST] Receptor for the leucine-rich nuclear export signal (NES). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The E571K mutation of CRM1 is highly prevalent in some cancers, but its mechanism of tumorigenesis is unclear. Glu571 of CRM1 is located in its NES-binding groove, suggesting binding of select NESs may be altered. We generated HEK-293 cells with either monoallelic CRM1WT/E571K or biallelic CRM1E571K/E571K using CRISPR/Cas9. We also combined analysis of binding affinities and structures of 27 diverse NESs for wild-type and E571K CRM1 with structure-based bioinformatics. While most NESs bind the two CRM1 similarly, NESs from Mek1, eIF4E-transporter and RPS2 showed >10-fold affinity differences. These NESs have multiple charged side chains binding close to CRM1 position 571, but this feature alone was not sufficient to predict different binding to CRM1(E571K). Consistent with eIF4E-transporterNES binding weaker to CRM1(E571K), eIF4E-transporter was mislocalized in tumor cells carrying CRM1(E571K). This serves as proof of concept that understanding how CRM1(E571K) affects NES-binding provides a platform for identifying cargos that are mislocalized in cancer upon CRM1 mutation. Lastly, we showed that large affinity changes seen with some NES peptides (of Mek1 and RPS2) do not always translate to the full-length cargos suggesting limitations with current NES prediction methods. Therefore, comprehensive studies like ours are imperative to identify CRM1 cargos with real pathogenic potential. | |||
Recognition of nuclear export signals by CRM1 carrying the oncogenic E571K mutation.,Baumhardt JM, Walker JS, Lee Y, Shakya B, Brautigam CA, Lapalombella R, Grishin N, Chook YM Mol Biol Cell. 2020 Jun 10:mbcE20040233. doi: 10.1091/mbc.E20-04-0233. PMID:32520643<ref>PMID:32520643</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6x2p" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Exportin 3D structures|Exportin 3D structures]] | |||
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Baumhardt JM]] | |||