View source for 9bkd


==The structure of human Pdcd4 bound to the 40S small ribosomal subunit==
<StructureSection load='9bkd' size='340' side='right'caption='[[9bkd]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bkd]] is a 10 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=9BKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BKD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.6&#8491;</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=9bkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bkd OCA], [https://pdbe.org/9bkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bkd RCSB], [https://www.ebi.ac.uk/pdbsum/9bkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bkd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RS6_HUMAN RS6_HUMAN] May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5' UTR of mRNA.

Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit.,Brito Querido J, Sokabe M, Diaz-Lopez I, Gordiyenko Y, Zuber P, Du Y, Albacete-Albacete L, Ramakrishnan V, Fraser CS Nat Commun. 2024 Aug 8;15(1):6633. doi: 10.1038/s41467-024-50672-8. PMID:39117603<ref>PMID:39117603</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bkd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Albacete-Albacete L]]
[[Category: Brito Querido J]]
[[Category: Diaz-Lopez I]]
[[Category: Gordiyenko Y]]
[[Category: Ramakrishnan V]]
[[Category: SFraser C]]
[[Category: Sokabe M]]
[[Category: Zuber P]]