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| | ==Crystal structure of RidL(1-200) complexed with VPS29== | | ==Crystal structure of RidL(1-200) complexed with VPS29== |
| - | <StructureSection load='5wyh' size='340' side='right' caption='[[5wyh]], [[Resolution|resolution]] 2.46Å' scene=''> | + | <StructureSection load='5wyh' size='340' side='right'caption='[[5wyh]], [[Resolution|resolution]] 2.46Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wyh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_570-co-h Legionella pneumophila subsp. pneumophila 570-co-h]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WYH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WYH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wyh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_ATCC_43290 Legionella pneumophila subsp. pneumophila ATCC 43290]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WYH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.46Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VPS29, DC15, DC7, MDS007 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), lp12_2303 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=933093 Legionella pneumophila subsp. pneumophila 570-CO-H])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyh OCA], [http://pdbe.org/5wyh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wyh RCSB], [http://www.ebi.ac.uk/pdbsum/5wyh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyh ProSAT]</span></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=5wyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyh OCA], [https://pdbe.org/5wyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wyh RCSB], [https://www.ebi.ac.uk/pdbsum/5wyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPS29_HUMAN VPS29_HUMAN]] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Has low protein phosphatase activity towards a serine-phosphorylated peptide derived from IGF2R (in vitro).<ref>PMID:15247922</ref> | + | [https://www.uniprot.org/uniprot/VPS29_HUMAN VPS29_HUMAN] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Has low protein phosphatase activity towards a serine-phosphorylated peptide derived from IGF2R (in vitro).<ref>PMID:15247922</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Retrograde vesicle trafficking pathways are responsible for returning membrane-associated components from endosomes to the Golgi apparatus and the endoplasmic reticulum (ER), and they are critical for maintaining organelle identity, lipid homeostasis, and many other cellular functions. The retrograde transport pathway has emerged as an important target for intravacuolar bacterial pathogens. The opportunistic pathogen Legionella pneumophila exploits both the secretory and recycling branches of the vesicle transport pathway for intracellular bacterial proliferation. Its Dot/Icm effector RidL inhibits the activity of the retromer by directly engaging retromer components. However, the mechanism underlying such inhibition remains unknown. Here we present the crystal structure of RidL in complex with VPS29, a subunit of the retromer. Our results demonstrate that RidL binds to a highly conserved hydrophobic pocket of VPS29. This interaction is critical for endosomal recruitment of RidL and for its inhibitory effects. RidL inhibits retromer activity by direct competition, in which it occupies the VPS29-binding site of the essential retromer regulator TBC1d5. The mechanism of retromer inhibition by RidL reveals a hotspot on VPS29 critical for recognition by its regulators that is also exploited by pathogens, and provides a structural basis for the development of small molecule inhibitors against the retromer.
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| - | Mechanism of inhibition of retromer transport by the bacterial effector RidL.,Yao J, Yang F, Sun X, Wang S, Gan N, Liu Q, Liu D, Zhang X, Niu D, Wei Y, Ma C, Luo ZQ, Sun Q, Jia D Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1446-E1454. doi:, 10.1073/pnas.1717383115. Epub 2018 Jan 31. PMID:29386389<ref>PMID:29386389</ref>
| + | ==See Also== |
| - | | + | *[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5wyh" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Legionella pneumophila subsp. pneumophila 570-co-h]] | + | [[Category: Large Structures]] |
| - | [[Category: Jia, D]] | + | [[Category: Legionella pneumophila subsp. pneumophila ATCC 43290]] |
| - | [[Category: Sun, Q]] | + | [[Category: Jia D]] |
| - | [[Category: Yao, J]] | + | [[Category: Sun Q]] |
| - | [[Category: Complex vps29 ridl]]
| + | [[Category: Yao J]] |
| - | [[Category: Metal binding protein-protein binding complex]]
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