9cjk
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human TMED9 octamer structure== | |
| + | <StructureSection load='9cjk' size='340' side='right'caption='[[9cjk]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9cjk]] is a 8 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=9CJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CJK 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]] 3.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9ED:[(2~{R})-2-[(~{E})-octadec-9-enoyl]oxy-3-[oxidanyl-[(1~{R},2~{R},3~{S},4~{R},5~{R},6~{S})-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl]+(~{E})-octadec-9-enoate'>9ED</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=9cjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9cjk OCA], [https://pdbe.org/9cjk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9cjk RCSB], [https://www.ebi.ac.uk/pdbsum/9cjk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9cjk ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TMED9_HUMAN TMED9_HUMAN] Appears to be involved in vesicular protein trafficking, mainly in the early secretory pathway. In COPI vesicle-mediated retrograde transport involved in the coatomer recruitment to membranes of the early secretory pathway. Increases coatomer-dependent activity of ARFGAP2. Thought to play a crucial role in the specific retention of p24 complexes in cis-Golgi membranes; specifically contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network. May be involved in organization of intracellular membranes, such as of the ER-Golgi intermediate compartment and the Golgi apparatus. Involved in ER localization of PTPN2 isoform PTPB.<ref>PMID:10852829</ref> <ref>PMID:14600267</ref> <ref>PMID:16595549</ref> <ref>PMID:18287528</ref> <ref>PMID:19296914</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Intracellular accumulation of misfolded proteins causes serious human proteinopathies. The transmembrane emp24 domain 9 (TMED9) cargo receptor promotes a general mechanism of cytotoxicity by entrapping misfolded protein cargos in the early secretory pathway. However, the molecular basis for this TMED9-mediated cargo retention remains elusive. Here, we report cryo-electron microscopy structures of TMED9, which reveal its unexpected self-oligomerization into octamers, dodecamers, and, by extension, even higher-order oligomers. The TMED9 oligomerization is driven by an intrinsic symmetry mismatch between the trimeric coiled coil domain and the tetrameric transmembrane domain. Using frameshifted Mucin 1 as an example of aggregated disease-related protein cargo, we implicate a mode of direct interaction with the TMED9 luminal Golgi-dynamics domain. The structures suggest and we confirm that TMED9 oligomerization favors the recruitment of coat protein I (COPI), but not COPII coatomers, facilitating retrograde transport and explaining the observed cargo entrapment. Our work thus reveals a molecular basis for TMED9-mediated misfolded protein retention in the early secretory pathway. | ||
| - | + | Molecular basis of TMED9 oligomerization and entrapment of misfolded protein cargo in the early secretory pathway.,Xiao L, Pi X, Goss AC, El-Baba T, Ehrmann JF, Grinkevich E, Bazua-Valenti S, Padovano V, Alper SL, Carey D, Udeshi ND, Carr SA, Pablo JL, Robinson CV, Greka A, Wu H Sci Adv. 2024 Sep 20;10(38):eadp2221. doi: 10.1126/sciadv.adp2221. Epub 2024 Sep , 20. PMID:39303030<ref>PMID:39303030</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Le | + | <div class="pdbe-citations 9cjk" style="background-color:#fffaf0;"></div> |
| - | [[Category: Xiong | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Le X]] | ||
| + | [[Category: Xiong P]] | ||
Current revision
Human TMED9 octamer structure
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