6ehr

From Proteopedia

The crystal structure of the human LAMTOR-RagA CTD-RagC CTD complex

PDB ID 6ehr

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Structural highlights

6ehr is a 7 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 2.898Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2]

Publication Abstract from PubMed

LAMTOR (Late endosomal and lysosomal adaptor and mitogen activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) activator) also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag GTPases associated with the pentamer through their C-terminal domains, predefining the orientation for interaction with mTORC1. In vitro reconstitution and experiments with site directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. Functional data validated the impact of two short LAMTOR1 amino acid regions in recruitment and stabilization of the Rag GTPases.

Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling.,de Araujo MEG, Naschberger A, Furnrohr BG, Stasyk T, Dunzendorfer-Matt T, Lechner S, Welti S, Kremser L, Shivalingaiah G, Offterdinger M, Lindner HH, Huber LA, Scheffzek K Science. 2017 Sep 21. pii: eaao1583. doi: 10.1126/science.aao1583. PMID:28935770^[3]

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

References

↑ 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
↑ 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
↑ de Araujo MEG, Naschberger A, Furnrohr BG, Stasyk T, Dunzendorfer-Matt T, Lechner S, Welti S, Kremser L, Shivalingaiah G, Offterdinger M, Lindner HH, Huber LA, Scheffzek K. Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling. Science. 2017 Sep 21. pii: eaao1583. doi: 10.1126/science.aao1583. PMID:28935770 doi:http://dx.doi.org/10.1126/science.aao1583