This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5gt8

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal Structure of apo-CASTOR1

Structural highlights

5gt8 is a 4 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 2.8Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAST1_HUMAN Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058). As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1 (PubMed:26972053, PubMed:27487210, PubMed:33594058). Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1-containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of metabolism and cell growth. Among the numerous extracellular and intracellular signals, certain amino acids activate mTORC1 in a Rag-dependent manner. Arginine can stimulate mTORC1 activity by releasing the inhibitor CASTOR1 (Cellular Arginine Sensor of mTORC1) from GATOR2, a positive regulator of mTORC1 which interacts with GATOR1, the GAP for RagA/B. Three groups have resolved the structures of arginine-CASTOR1 complex, shedding a new light on molecular basis of the regulation of mTORC1 activity by arginine. However, lacking the apo structure of CASTOR1 prelimited the molecular understanding of mechanism underlying mTORC1 regulation. Here, we report crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states at 2.05A and 2.8A, respectively. Structural comparison of CASTOR1 between two states reveals near identical conformations, except in two loop regions. It indicates CASTOR1 does not undergo large conformational change during arginine binding. Therefore, we conclude a detailed structural interpretation of arginine sensing by CASTOR1 in mTORC1 pathway.

Crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states.,Zhou Y, Wang C, Xiao Q, Guo L Biochem Biophys Res Commun. 2019 Jan 8;508(2):387-391. doi:, 10.1016/j.bbrc.2018.11.147. Epub 2018 Nov 28. PMID:30503338^[4]

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

References

↑ Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, Wyant GA, Wang T, Harper JW, Gygi SP, Sabatini DM. The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell. 2016 Mar 24;165(1):153-64. doi: 10.1016/j.cell.2016.02.035. Epub 2016 Mar, 10. PMID:26972053 doi:http://dx.doi.org/10.1016/j.cell.2016.02.035
↑ Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM. Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Nature. 2016 Aug 11;536(7615):229-33. PMID:27487210 doi:http://dx.doi.org/10.1038/nature19079
↑ Li T, Wang X, Ju E, da Silva SR, Chen L, Zhang X, Wei S, Gao SJ. RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation. Nat Commun. 2021 Feb 16;12(1):1055. PMID:33594058 doi:10.1038/s41467-021-21206-3
↑ Zhou Y, Wang C, Xiao Q, Guo L. Crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states. Biochem Biophys Res Commun. 2019 Jan 8;508(2):387-391. doi:, 10.1016/j.bbrc.2018.11.147. Epub 2018 Nov 28. PMID:30503338 doi:http://dx.doi.org/10.1016/j.bbrc.2018.11.147

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5gt8"

Categories: Homo sapiens | Large Structures | Deng D | Guo L

@@ Line 3: / Line 3: @@
 <StructureSection load='5gt8' size='340' side='right'caption='[[5gt8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5gt8]] is a 4 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=5GT8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GT8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5gt8]] is a 4 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=5GT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GT8 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gt7|5gt7]]</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]] 2.8&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GATSL3, CASTOR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5gt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gt8 OCA], [https://pdbe.org/5gt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gt8 RCSB], [https://www.ebi.ac.uk/pdbsum/5gt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gt8 ProSAT]</span></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=5gt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gt8 OCA], [http://pdbe.org/5gt8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gt8 RCSB], [http://www.ebi.ac.uk/pdbsum/5gt8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gt8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GATL3_HUMAN GATL3_HUMAN]] Functions as an intracellular arginine sensor that regulates the TORC1 signaling pathway through the GATOR complex. As a homooligomer or a heterooligomer with GATSL2, directly binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of arginine to GATSL3 disrupts the interaction of GATSL3-containing oligomers with GATOR2 and activates the TORC1 signaling pathway.<ref>PMID:26972053</ref>
+[https://www.uniprot.org/uniprot/CAST1_HUMAN CAST1_HUMAN] Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058). As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1 (PubMed:26972053, PubMed:27487210, PubMed:33594058). Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1-containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058).<ref>PMID:26972053</ref> <ref>PMID:27487210</ref> <ref>PMID:33594058</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Deng, D]]
+[[Category: Deng D]]
-[[Category: Guo, L]]
+[[Category: Guo L]]
-[[Category: Act domain]]
-[[Category: Arginine binding]]
-[[Category: Castor1]]
-[[Category: Gator2]]
-[[Category: Gatsl2]]
-[[Category: Mtor]]
-[[Category: Signaling protein]]

5gt8

From Proteopedia

Current revision

Crystal Structure of apo-CASTOR1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox