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-Structure paper
Title | Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 1012, Year 2023 |
Publish date | Feb 23, 2023 |
Authors | Jiale 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 Abstract | 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- ...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 links | Nat Commun / PubMed:36823105 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.76 Å |
Structure data | EMDB-33479, PDB-7xv3: |
Chemicals | ChemComp-WJS: ChemComp-HOH: |
Source |
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Keywords | MEMBRANE PROTEIN / GPCR |