|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of Ragulator== | | ==Crystal structure of Ragulator== |
| - | <StructureSection load='6b9x' size='340' side='right' caption='[[6b9x]], [[Resolution|resolution]] 1.42Å' scene=''> | + | <StructureSection load='6b9x' size='340' side='right'caption='[[6b9x]], [[Resolution|resolution]] 1.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6b9x]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B9X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b9x]] is a 5 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=6B9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B9X FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LAMTOR1, C11orf59, PDRO, PP7157 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LAMTOR2, MAPBPIP, ROBLD3, HSPC003 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LAMTOR3, MAP2K1IP1, MAPKSP1, PRO2783 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LAMTOR4, C7orf59 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LAMTOR5, HBXIP, hCG_40252 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.42Å</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=6b9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b9x OCA], [http://pdbe.org/6b9x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b9x RCSB], [http://www.ebi.ac.uk/pdbsum/6b9x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b9x 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=6b9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b9x OCA], [https://pdbe.org/6b9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b9x RCSB], [https://www.ebi.ac.uk/pdbsum/6b9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b9x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/LTOR2_HUMAN LTOR2_HUMAN]] Primary immunodeficiency syndrome due to p14 deficiency. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LTOR4_HUMAN LTOR4_HUMAN]] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated.<ref>PMID:22980980</ref> [[http://www.uniprot.org/uniprot/LTOR1_HUMAN LTOR1_HUMAN]] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation.<ref>PMID:19654316</ref> <ref>PMID:20381137</ref> <ref>PMID:20544018</ref> <ref>PMID:22980980</ref> [[http://www.uniprot.org/uniprot/LTOR3_HUMAN LTOR3_HUMAN]] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.<ref>PMID:20381137</ref> <ref>PMID:22980980</ref> [[http://www.uniprot.org/uniprot/LTOR2_HUMAN LTOR2_HUMAN]] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.<ref>PMID:20381137</ref> <ref>PMID:22980980</ref> | + | [https://www.uniprot.org/uniprot/LTOR1_HUMAN LTOR1_HUMAN] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation.<ref>PMID:19654316</ref> <ref>PMID:20381137</ref> <ref>PMID:20544018</ref> <ref>PMID:22980980</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6b9x" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6b9x" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ragulator complex|Ragulator complex]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hurley, J H]] | + | [[Category: Large Structures]] |
| - | [[Category: SU, M Y]] | + | [[Category: Hurley JH]] |
| - | [[Category: Lamtor]] | + | [[Category: SU M-Y]] |
| - | [[Category: Ragulator]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
LTOR1_HUMAN As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation.[1] [2] [3] [4]
Publication Abstract from PubMed
The lysosomal membrane is the locus for sensing cellular nutrient levels, which are transduced to mTORC1 via the Rag GTPases and the Ragulator complex. The crystal structure of the five-subunit human Ragulator at 1.4 A resolution was determined. Lamtor1 wraps around the other four subunits to stabilize the assembly. The Lamtor2:Lamtor3 dimer stacks upon Lamtor4:Lamtor5 to create a platform for Rag binding. Hydrogen-deuterium exchange was used to map the Rag binding site to the outer face of the Lamtor2:Lamtor3 dimer and to the N-terminal intrinsically disordered region of Lamtor1. EM was used to reconstruct the assembly of the full-length RagAGTP:RagCGDP dimer bound to Ragulator at 16 A resolution, revealing that the G-domains of the Rags project away from the Ragulator core. The combined structural model shows how Ragulator functions as a platform for the presentation of active Rags for mTORC1 recruitment, and might suggest an unconventional mechanism for Rag GEF activity.
Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex.,Su MY, Morris KL, Kim DJ, Fu Y, Lawrence R, Stjepanovic G, Zoncu R, Hurley JH Mol Cell. 2017 Oct 25. pii: S1097-2765(17)30791-8. doi:, 10.1016/j.molcel.2017.10.016. PMID:29107538[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hoshino D, Tomari T, Nagano M, Koshikawa N, Seiki M. A novel protein associated with membrane-type 1 matrix metalloproteinase binds p27(kip1) and regulates RhoA activation, actin remodeling, and matrigel invasion. J Biol Chem. 2009 Oct 2;284(40):27315-26. doi: 10.1074/jbc.M109.041400. Epub 2009, Aug 4. PMID:19654316 doi:http://dx.doi.org/10.1074/jbc.M109.041400
- ↑ Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr , 8. PMID:20381137 doi:10.1016/j.cell.2010.02.024
- ↑ Guillaumot P, Luquain C, Malek M, Huber AL, Brugiere S, Garin J, Grunwald D, Regnier D, Petrilli V, Lefai E, Manie SN. Pdro, a protein associated with late endosomes and lysosomes and implicated in cellular cholesterol homeostasis. PLoS One. 2010 Jun 8;5(6):e10977. doi: 10.1371/journal.pone.0010977. PMID:20544018 doi:http://dx.doi.org/10.1371/journal.pone.0010977
- ↑ Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell. 2012 Sep 14;150(6):1196-208. doi: 10.1016/j.cell.2012.07.032. PMID:22980980 doi:10.1016/j.cell.2012.07.032
- ↑ Su MY, Morris KL, Kim DJ, Fu Y, Lawrence R, Stjepanovic G, Zoncu R, Hurley JH. Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex. Mol Cell. 2017 Oct 25. pii: S1097-2765(17)30791-8. doi:, 10.1016/j.molcel.2017.10.016. PMID:29107538 doi:http://dx.doi.org/10.1016/j.molcel.2017.10.016
|
