신진우 (포항공과대학교) | 한빛사논문 > 한빛사

한빛사논문

조회887

신진우Jinwoo Shin

포항공과대학교

CV File 40 kb

Nat. Struct. Mol. Biol., Feb 08 2024, | https://doi.org/10.1038/s41594-024-01224-7 Constitutive activation mechanism of a class C GPCR

Jinwoo Shin^1,14, Junhyeon Park^1,14, Jieun Jeong², Jordy Homing Lam^3,4, Xingyu Qiu^5,6, Di Wu^5,6, Kuglae Kim⁷, Joo-Youn Lee⁸, Carol V. Robinson^5,6, Jaekyung Hyun⁹, Vsevolod Katritch^3,4,10,11, Kwang Pyo Kim^2,12 & Yunje Cho^1,13

¹Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.

²Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin, Republic of Korea.

³Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA.

⁴Bridge Institute and Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.

⁵Department of Chemistry, University of Oxford, Oxford, UK.

⁶Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.

⁷Department of Pharmacy, Yonsei University, Incheon, Republic of Korea.

⁸Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea.

⁹School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.

¹⁰Center for New Technologies in Drug Discovery and Development, University of Southern California, Los Angeles, CA, USA.

¹¹Department of Chemistry, University of Southern California, Los Angeles, CA, USA.

¹²Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, Republic of Korea.

¹³Department of Medical Science and Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea.

¹⁴These authors contributed equally: Jinwoo Shin, Junhyeon Park.

Corresponding authors : Correspondence to Kwang Pyo Kim or Yunje Cho.

Abstract

Class C G-protein-coupled receptors (GPCRs) are activated through binding of agonists to the large extracellular domain (ECD) followed by rearrangement of the transmembrane domains (TMDs). GPR156, a class C orphan GPCR, is unique because it lacks an ECD and exhibits constitutive activity. Impaired GPR156-G _i signaling contributes to loss of hearing. Here we present the cryo-electron microscopy structures of human GPR156 in the G _o-free and G _o-coupled states. We found that an endogenous phospholipid molecule is located within each TMD of the GPR156 dimer. Asymmetric binding of Gα to the phospholipid-bound GPR156 dimer restructures the first and second intracellular loops and the carboxy-terminal part of the elongated transmembrane 7 (TM7) without altering dimer conformation. Our findings reveal that GPR156 is a transducer for phospholipid signaling. Constant binding of abundant phospholipid molecules and the G-protein-induced reshaping of the cytoplasmic face provide a basis for the constitutive activation of GPR156.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-13)
연구진국내 연구진
분야 생명과학 > 구조생물 및 생물물리학

댓글 작성 로그인

CV 열람하기

연락처 보기