Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation

Jiale Liang, Asuka Inoue (), Tatsuya Ikuta, Ruixue Xia, Na Wang, Kouki Kawakami, Zhenmei Xu, Yu Qian, Xinyan Zhu, Anqi Zhang, Changyou Guo, Zhiwei Huang and Yuanzheng He ()
Additional contact information
Jiale Liang: Harbin Institute of Technology
Asuka Inoue: Tohoku University
Tatsuya Ikuta: Tohoku University
Ruixue Xia: Harbin Institute of Technology
Na Wang: Harbin Institute of Technology
Kouki Kawakami: Tohoku University
Zhenmei Xu: Harbin Institute of Technology
Yu Qian: Harbin Institute of Technology
Xinyan Zhu: Harbin Institute of Technology
Anqi Zhang: Harbin Institute of Technology
Changyou Guo: Harbin Institute of Technology
Zhiwei Huang: Harbin Institute of Technology
Yuanzheng He: Harbin Institute of Technology

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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 Gs 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 Gs 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36575-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36575-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36575-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().