View source for 9lhx


==Rigid fitting model of GPR155 extended dimer==
<StructureSection load='9lhx' size='340' side='right'caption='[[9lhx]], [[Resolution|resolution]] 5.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9lhx]] is a 2 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=9LHX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LHX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.62&#8491;</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=9lhx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lhx OCA], [https://pdbe.org/9lhx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lhx RCSB], [https://www.ebi.ac.uk/pdbsum/9lhx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lhx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LYCHS_HUMAN LYCHS_HUMAN] Cholesterol-binding protein that acts as a regulator of mTORC1 signaling pathway (PubMed:36007018). Acts as a sensor of cholesterol to signal cholesterol sufficiency to mTORC1: in presence of cholesterol, binds cholesterol, leading to disrupt interaction between the GATOR1 and KICSTOR complexes and promote mTORC1 signaling (PubMed:36007018). Upon cholesterol starvation, GPR155/LYCHOS is unable to perturb the association between GATOR1 and KICSTOR, leading to mTORC1 signaling inhibition (PubMed:36007018).<ref>PMID:36007018</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cholesterol (CHL) serves as a building block for membrane biogenesis and a precursor to oxysterols, steroid hormones, bile acids, and vitamin D. The lysosome serves as a major sorting station for low-density lipoproteins (LDLs), which carry dietary CHL, and it is also the cellular site where the master growth regulator, the protein kinase mechanistic Target of Rapamycin Complex 1 (mTORC1), is activated. Recently, the lysosomal transmembrane protein GPR155 was reported to signals CHL sufficiency to mTORC1 through sequestration of the GTPase-activating protein towards the Rags 1 (GATOR1). Although the recently reported structures of GPR155 have revealed the CHL binding site, how the signal is transduced from the CHL binding site to the soluble parts of GPR155 and GATOR1 remains unknown. Here, with our three cryo-EM structures of GPR155 captured in different conformations in complex with CHL, complemented by long-time scale molecular dynamics simulations, the dynamic rearrangement of different domains was observed. CHL binding induces a widening of the crevice between the transporter and GPCR domains. The extending helix preceding transmembrane helix (TM) 16, which was unresolved in other structures, acts as a linkage lever that transmits the rotation of the GPCR domain to the soluble parts of GPR155 in response to CHL binding. This work not only answers the question of how CHL is sensed by GPR155, but also addresses a more profound question: how the signal perceived by the TMs regions is transduced to the LED and DEP domains.

Structural insight into GPR155-mediated cholesterol sensing and signal transduction.,Li D, Zhang X, Feng J, Xie Y, Han P, He M, Hao L, Guo T, Bai X, Yuan K, Sun J, Pang X, Wu Y, Liu Y, Gao GF, Huang N, Xiao H, Gao F Sci Bull (Beijing). 2025 Nov 15;70(21):3625-3637. doi: , 10.1016/j.scib.2025.09.012. Epub 2025 Sep 10. PMID:41058362<ref>PMID:41058362</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9lhx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gao F]]
[[Category: Han P]]
[[Category: Li D]]
[[Category: Zhang X]]