5y3a: Difference between revisions

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<StructureSection load='5y3a' size='340' side='right'caption='[[5y3a]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
<StructureSection load='5y3a' size='340' side='right'caption='[[5y3a]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5y3a]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y3A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Y3A FirstGlance]. <br>
<table><tr><td colspan='2'>[[5y3a]] 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=5Y3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y3A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.9&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5y38|5y38]], [[5y39|5y39]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5y3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y3a OCA], [http://pdbe.org/5y3a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y3a RCSB], [http://www.ebi.ac.uk/pdbsum/5y3a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y3a 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=5y3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y3a OCA], [https://pdbe.org/5y3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y3a RCSB], [https://www.ebi.ac.uk/pdbsum/5y3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y3a 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>  [[http://www.uniprot.org/uniprot/LTOR5_HUMAN LTOR5_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. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway. Down-regulates hepatitis B virus (HBV) replication.<ref>PMID:12773388</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 ==
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==See Also==
==See Also==
*[[Ragulator complex|Ragulator complex]]
*[[Ragulator complex 3D structures|Ragulator complex 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Ding, J]]
[[Category: Ding J]]
[[Category: Zhang, T]]
[[Category: Zhang T]]
[[Category: Lamtor]]
[[Category: Ragulator complex]]
[[Category: Signaling protein]]

Latest revision as of 11:20, 22 November 2023

Crystal structure of Ragulator complex (p18 49-161)Crystal structure of Ragulator complex (p18 49-161)

Structural highlights

5y3a is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Amino acid-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) is mediated by Rag GTPases, which are recruited to the lysosome by the Ragulator complex consisting of p18, MP1, p14, HBXIP and C7orf59; however, the molecular mechanism is elusive. Here, we report the crystal structure of Ragulator, in which p18 wraps around the MP1-p14 and C7orf59-HBXIP heterodimers and the interactions of p18 with MP1, C7orf59, and HBXIP are essential for the assembly of Ragulator. There are two binding sites for the Roadblock domains of Rag GTPases: helix alpha1 of p18 and the two helices side of MP1-p14. The interaction of Ragulator with Rag GTPases is required for their cellular co-localization and can be competitively inhibited by C17orf59. Collectively, our data indicate that Ragulator functions as a scaffold to recruit Rag GTPases to lysosomal membrane in mTORC1 signaling.

Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1.,Zhang T, Wang R, Wang Z, Wang X, Wang F, Ding J Nat Commun. 2017 Nov 9;8(1):1394. doi: 10.1038/s41467-017-01567-4. PMID:29123114[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Zhang T, Wang R, Wang Z, Wang X, Wang F, Ding J. Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1. Nat Commun. 2017 Nov 9;8(1):1394. doi: 10.1038/s41467-017-01567-4. PMID:29123114 doi:http://dx.doi.org/10.1038/s41467-017-01567-4

5y3a, resolution 2.90Å

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