We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

5i2c

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:33, 6 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 3: Line 3:
<StructureSection load='5i2c' size='340' side='right'caption='[[5i2c]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='5i2c' size='340' side='right'caption='[[5i2c]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5i2c]] 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=5I2C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I2C FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5i2c]] 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=5I2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I2C FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ARG:ARGININE'>ARG</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]] 1.801&#8491;</td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GATSL3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ARG:ARGININE'>ARG</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=5i2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2c OCA], [http://pdbe.org/5i2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i2c RCSB], [http://www.ebi.ac.uk/pdbsum/5i2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2c 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=5i2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2c OCA], [https://pdbe.org/5i2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i2c RCSB], [https://www.ebi.ac.uk/pdbsum/5i2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2c ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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 ==
+
-
The mechanistic Target of Rapamycin Complex 1 (mTORC1) is a major regulator of eukaryotic growth that coordinates anabolic and catabolic cellular processes with inputs such as growth factors and nutrients, including amino acids. In mammals arginine is particularly important, promoting diverse physiological effects such as immune cell activation, insulin secretion, and muscle growth, largely mediated through activation of mTORC1 (refs 4, 5, 6, 7). Arginine activates mTORC1 upstream of the Rag family of GTPases, through either the lysosomal amino acid transporter SLC38A9 or the GATOR2-interacting Cellular Arginine Sensor for mTORC1 (CASTOR1). However, the mechanism by which the mTORC1 pathway detects and transmits this arginine signal has been elusive. Here, we present the 1.8 A crystal structure of arginine-bound CASTOR1. Homodimeric CASTOR1 binds arginine at the interface of two Aspartate kinase, Chorismate mutase, TyrA (ACT) domains, enabling allosteric control of the adjacent GATOR2-binding site to trigger dissociation from GATOR2 and downstream activation of mTORC1. Our data reveal that CASTOR1 shares substantial structural homology with the lysine-binding regulatory domain of prokaryotic aspartate kinases, suggesting that the mTORC1 pathway exploited an ancient, amino-acid-dependent allosteric mechanism to acquire arginine sensitivity. Together, these results establish a structural basis for arginine sensing by the mTORC1 pathway and provide insights into the evolution of a mammalian nutrient sensor.
+
-
 
+
-
Mechanism of arginine sensing by CASTOR1 upstream of mTORC1.,Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM Nature. 2016 Aug 11;536(7615):229-33. PMID:27487210<ref>PMID:27487210</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5i2c" style="background-color:#fffaf0;"></div>
+
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Knockenhauer, K E]]
+
[[Category: Knockenhauer KE]]
-
[[Category: Saxton, R A]]
+
[[Category: Saxton RA]]
-
[[Category: Schwartz, T U]]
+
[[Category: Schwartz TU]]
-
[[Category: Act]]
+
-
[[Category: Arginine]]
+
-
[[Category: Mtor]]
+
-
[[Category: Signaling]]
+
-
[[Category: Signaling protein]]
+

Current revision

Arginine-bound CASTOR1 from Homo sapiens

PDB ID 5i2c

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5i2c"
Personal tools