9bln
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex== |
| + | <StructureSection load='9bln' size='340' side='right'caption='[[9bln]], [[Resolution|resolution]] 3.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9bln]] 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=9BLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BLN 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]] 3.9Å</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=9bln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bln OCA], [https://pdbe.org/9bln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bln RCSB], [https://www.ebi.ac.uk/pdbsum/9bln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bln ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/EIF3I_HUMAN EIF3I_HUMAN] Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773).[HAMAP-Rule:MF_03008]<ref>PMID:17581632</ref> <ref>PMID:25849773</ref> <ref>PMID:27462815</ref> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9bln" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Diaz-Lopez | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: Ramakrishnan | + | </StructureSection> |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Albacete-Albacete L]] |
| - | [[Category: | + | [[Category: Brito Querido J]] |
| + | [[Category: Diaz-Lopez I]] | ||
| + | [[Category: Gordiyenko Y]] | ||
| + | [[Category: Ramakrishnan V]] | ||
| + | [[Category: S Fraser C]] | ||
| + | [[Category: Sokabe M]] | ||
| + | [[Category: Yifei D]] | ||
| + | [[Category: Zuber P]] | ||
Current revision
The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex
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