View source for 8phv


==Structure of Human selenomethionylated Cdc123 bound to domain 3 of eIF2 gamma==
<StructureSection load='8phv' size='340' side='right'caption='[[8phv]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8phv]] is a 4 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=8PHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PHV 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]] 1.97&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=8phv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8phv OCA], [https://pdbe.org/8phv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8phv RCSB], [https://www.ebi.ac.uk/pdbsum/8phv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8phv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD123_HUMAN CD123_HUMAN] ATP-dependent protein-folding chaperone for the eIF2 complex (PubMed:35031321, PubMed:37507029). Binds to the gamma subunit of the eIF2 complex which allows the subunit to assemble with the alpha and beta subunits (By similarity).[UniProtKB:Q05791]<ref>PMID:35031321</ref> <ref>PMID:37507029</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Eukaryotic initiation factor 2 (eIF2) plays a key role in protein synthesis and in its regulation. The assembly of this heterotrimeric factor is facilitated by Cdc123, a member of the ATP grasp family that binds the gamma subunit of eIF2. Notably, some mutations related to MEHMO syndrome, an X-linked intellectual disability, affect Cdc123-mediated eIF2 assembly. The mechanism of action of Cdc123 is unclear and structural information for the human protein is awaited. Here, the crystallographic structure of human Cdc123 (Hs-Cdc123) bound to domain 3 of human eIF2gamma (Hs-eIF2gammaD3) was determined. The structure shows that the domain 3 of eIF2gamma is bound to domain 1 of Cdc123. In addition, the long C-terminal region of Hs-Cdc123 provides a link between the ATP and Hs-eIF2gammaD3 binding sites. A thermal shift assay shows that ATP is tightly bound to Cdc123 whereas the affinity of ADP is much smaller. Yeast cell viability experiments, western blot analysis and two-hybrid assays show that ATP is important for the function of Hs-Cdc123 in eIF2 assembly. These data and recent findings allow us to propose a refined model to explain the mechanism of action of Cdc123 in eIF2 assembly.

Binding of human Cdc123 to eIF2gamma.,Cardenal Peralta C, Vandroux P, Neumann-Arnold L, Panvert M, Fagart J, Seufert W, Mechulam Y, Schmitt E J Struct Biol. 2023 Sep;215(3):108006. doi: 10.1016/j.jsb.2023.108006. Epub 2023 , Jul 27. PMID:37507029<ref>PMID:37507029</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8phv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cardenal Peralta C]]
[[Category: Fagart J]]
[[Category: Mechulam Y]]
[[Category: Schmitt E]]
[[Category: Seufert W]]