7XV3

Cryo-EM structure of LPS-bound GPR174 in complex with Gs protein

Summary for 7XV3

• Entry DOI: 10.2210/pdb7xv3/pdb
• EMDB information: 33479
• Descriptor: Probable G-protein coupled receptor 174, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Engineered G protein subunit S (mini-Gs), ... (7 entities in total)
• Functional Keywords: gpcr, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 144074.61

Authors

He, Y.,Liang, J. (deposition date: 2022-05-20, release date: 2023-02-15, Last modification date: 2024-11-13)

Primary citation

Liang, J.,Inoue, A.,Ikuta, T.,Xia, R.,Wang, N.,Kawakami, K.,Xu, Z.,Qian, Y.,Zhu, X.,Zhang, A.,Guo, C.,Huang, Z.,He, Y.
Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation.
Nat Commun, 14:1012-1012, 2023

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-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.

PubMed: 36823105
DOI: 10.1038/s41467-023-36575-0

Experimental method

ELECTRON MICROSCOPY (2.76 Å)