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==Crystal Structure of MVM NS2 NES Peptide in complex with CRM1-Ran-RanBP1== | ==Crystal Structure of MVM NS2 NES Peptide in complex with CRM1-Ran-RanBP1== | ||
<StructureSection load='6cit' size='340' side='right' caption='[[6cit]], [[Resolution|resolution]] 2.03Å' scene=''> | <StructureSection load='6cit' size='340' side='right'caption='[[6cit]], [[Resolution|resolution]] 2.03Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cit]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIT OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6cit]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Minute_virus_of_mice Minute virus of mice] 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=6CIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CIT FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.027Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=6cit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cit OCA], [https://pdbe.org/6cit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cit RCSB], [https://www.ebi.ac.uk/pdbsum/6cit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cit ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/RAN_HUMAN RAN_HUMAN] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref> Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CRM1 (Exportin1/XPO1) exports hundreds of broadly functioning protein cargos out of the cell nucleus by binding to their classical nuclear export signals (NESs). The 8-15 amino acids long NESs contain 4-5 hydrophobic residues and are highly diverse in both sequence and CRM1-bound structure. Here, we examine the relationship between nuclear export activities of 24 different NES peptides in cells, and their CRM1-NES affinities. We found that binding affinity and nuclear export activity are linearly correlated for NESs with dissociation constants (KDs) between tens of nanomolar to tens of micromolar. NESs with KDs outside this range have significantly reduced nuclear export activities. These include two unusually tight-binding peptides, one from the nonstructural protein 2 of murine minute virus (MVM NS2) and the other a mutant of the Protein Kinase A Inhibitor (PKI) NES. The crystal structure of CRM1-bound MVM NS2(NES) suggests that extraordinarily tight CRM1 binding arises from intramolecular contacts within the NES that likely stabilizes the CRM1-bound conformation in free peptides. This mechanistic understanding led to the design of two novel peptide inhibitors that bind CRM1 with picomolar affinity. | |||
Correlation of CRM1-NES affinity with nuclear export activity.,Fu SC, Fung HYJ, Cagatay T, Baumhardt J, Chook YM Mol Biol Cell. 2018 Jun 21:mbcE18020096. doi: 10.1091/mbc.E18-02-0096. PMID:29927350<ref>PMID:29927350</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6cit" 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 == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Minute virus of mice]] | ||
[[Category: | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: | [[Category: Chook YM]] | ||
[[Category: | [[Category: Fung HYJ]] | ||