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TitleStructural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1012, Year 2023
Publish dateFeb 23, 2023
AuthorsJiale Liang / Asuka Inoue / Tatsuya Ikuta / Ruixue Xia / Na Wang / Kouki Kawakami / Zhenmei Xu / Yu Qian / Xinyan Zhu / Anqi Zhang / Changyou Guo / Zhiwei Huang / Yuanzheng He /
PubMed AbstractLysophosphatidylserine (LysoPS) is a lipid mediator that induces multiple cellular responses through binding to GPR174. Here, we present the cryo-electron microscopy (cryo-EM) structure of LysoPS- ...Lysophosphatidylserine (LysoPS) is a lipid mediator that induces multiple cellular responses through binding to GPR174. Here, we present the cryo-electron microscopy (cryo-EM) structure of LysoPS-bound human GPR174 in complex with G protein. The structure reveals a ligand recognition mode, including the negatively charged head group of LysoPS forms extensive polar interactions with surrounding key residues of the ligand binding pocket, and the L-serine moiety buries deeply into a positive charged cavity in the pocket. In addition, the structure unveils a partially open pocket on transmembrane domain helix (TM) 4 and 5 for a lateral entry of ligand. Finally, the structure reveals a G engaging mode featured by a deep insertion of a helix 5 (αH5) and extensive polar interactions between receptor and αH5. Taken together, the information revealed by our structural study provides a framework for understanding LysoPS signaling and a rational basis for designing LysoPS receptor-targeting drugs.
External linksNat Commun / PubMed:36823105 / PubMed Central
MethodsEM (single particle)
Resolution2.76 Å
Structure data

EMDB-33479, PDB-7xv3:
Cryo-EM structure of LPS-bound GPR174 in complex with Gs protein
Method: EM (single particle) / Resolution: 2.76 Å

Chemicals

ChemComp-WJS:
(2~{S})-2-$l^{4}-azanyl-3-[[(2~{R})-3-octadecanoyloxy-2-oxidanyl-propoxy]-oxidanyl-oxidanylidene-$l^{6}-phosphanyl]oxy-propanoic acid

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • lama glama (llama)
KeywordsMEMBRANE PROTEIN / GPCR

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