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| | ==Structure of Orp1L/Rab7 complex== | | ==Structure of Orp1L/Rab7 complex== |
| - | <StructureSection load='5z2m' size='340' side='right' caption='[[5z2m]], [[Resolution|resolution]] 2.14Å' scene=''> | + | <StructureSection load='5z2m' size='340' side='right'caption='[[5z2m]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5z2m]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z2M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5z2m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z2M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.142Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Osbpl1a, Orp1, Orp1a, Orp1l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rab7a, Rab7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5z2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z2m OCA], [http://pdbe.org/5z2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z2m RCSB], [http://www.ebi.ac.uk/pdbsum/5z2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z2m 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=5z2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z2m OCA], [https://pdbe.org/5z2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z2m RCSB], [https://www.ebi.ac.uk/pdbsum/5z2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z2m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OSBL1_MOUSE OSBL1_MOUSE]] Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A. Binds 25-hydroxycholesterol and cholesterol.[UniProtKB:Q9BXW6] [[http://www.uniprot.org/uniprot/RAB7A_MOUSE RAB7A_MOUSE]] Key regulator in endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and Mycobacteria. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA. Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation (By similarity). Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway (PubMed:23708524). Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).[UniProtKB:P51149]<ref>PMID:23708524</ref> | + | [https://www.uniprot.org/uniprot/OSBL1_MOUSE OSBL1_MOUSE] Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A. Binds 25-hydroxycholesterol and cholesterol.[UniProtKB:Q9BXW6] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5z2m" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5z2m" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, H H]] | + | [[Category: Mus musculus]] |
| - | [[Category: Li, J]] | + | [[Category: Li HH]] |
| - | [[Category: Liang, H H]] | + | [[Category: Li J]] |
| - | [[Category: Liu, K]] | + | [[Category: Liang HH]] |
| - | [[Category: Ma, X L]] | + | [[Category: Liu K]] |
| - | [[Category: Yang, C L]] | + | [[Category: Ma XL]] |
| - | [[Category: Complex]]
| + | [[Category: Yang CL]] |
| - | [[Category: Effector]]
| + | |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Gtpase]]
| + | |
| Structural highlights
Function
OSBL1_MOUSE Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A. Binds 25-hydroxycholesterol and cholesterol.[UniProtKB:Q9BXW6]
Publication Abstract from PubMed
Endosomal transport represents the primary mode for intracellular trafficking and signaling transduction and thus has to be tightly controlled. The molecular processes controlling the endosomal positioning utilize several large protein complexes, one of which contains the small GTPase Rab7, Rab-interacting lysosomal protein (RILP), and oxysterol-binding protein-related protein 1 (ORP1L). Rab7 is known to interact with RILP through a canonical binding site termed the effector-interacting switch region, but it is not clear how Rab7 interacts with ORP1L, limiting our understanding of the overall process. Here, we report structural and biochemical investigation of the Rab7-ORP1L interaction. We found that, contrary to prior studies, the interaction between Rab7 and the N-terminal ankyrin repeat domain (ARDN) of ORP1L is independent of Rab7's GTP- or GDP-binding state. Moreover, we show that Rab7 interacts with ORP1L ARDN via a unique region consisting of helix3 (alpha3) and 310-helix 2 (eta2). This architecture leaves the canonical effector-interacting switch regions available for RILP binding and thus allows formation of the ORP1L-Rab7-RILP tripartite complex. Mutational disruption of the interacting interface between ORP1L and Rab7 compromised the ability of ORP1L-Rab7-RILP to regulate the late endosome positioning. Collectively, our results again manifested the versatility in the interaction between GTPase and its effector.
A non-canonical GTPase interaction enables ORP1L-Rab7-RILP complex formation and late endosome positioning.,Ma X, Liu K, Li J, Li H, Li J, Liu Y, Yang C, Liang H J Biol Chem. 2018 Sep 7;293(36):14155-14164. doi: 10.1074/jbc.RA118.001854. Epub , 2018 Jul 16. PMID:30012887[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ma X, Liu K, Li J, Li H, Li J, Liu Y, Yang C, Liang H. A non-canonical GTPase interaction enables ORP1L-Rab7-RILP complex formation and late endosome positioning. J Biol Chem. 2018 Sep 7;293(36):14155-14164. doi: 10.1074/jbc.RA118.001854. Epub , 2018 Jul 16. PMID:30012887 doi:http://dx.doi.org/10.1074/jbc.RA118.001854
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