Author
Listed:
- Can Cao
(University of North Carolina at Chapel Hill School of Medicine)
- Hye Jin Kang
(University of North Carolina at Chapel Hill School of Medicine)
- Isha Singh
(University of California San Francisco, School of Medicine)
- He Chen
(Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)
- Chengwei Zhang
(Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)
- Wenlei Ye
(University of California, San Francisco)
- Byron W. Hayes
(Duke University Medical Center)
- Jing Liu
(Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)
- Ryan H. Gumpper
(University of North Carolina at Chapel Hill School of Medicine)
- Brian J. Bender
(University of California San Francisco, School of Medicine)
- Samuel T. Slocum
(University of North Carolina at Chapel Hill School of Medicine)
- Brian E. Krumm
(University of North Carolina at Chapel Hill School of Medicine)
- Katherine Lansu
(University of North Carolina at Chapel Hill School of Medicine)
- John D. McCorvy
(University of North Carolina at Chapel Hill School of Medicine
Medical College of Wisconsin)
- Wesley K. Kroeze
(University of North Carolina at Chapel Hill School of Medicine)
- Justin G. English
(University of North Carolina at Chapel Hill School of Medicine
University of Utah School of Medicine)
- Jeffrey F. DiBerto
(University of North Carolina at Chapel Hill School of Medicine)
- Reid H. J. Olsen
(University of North Carolina at Chapel Hill School of Medicine)
- Xi-Ping Huang
(University of North Carolina at Chapel Hill School of Medicine)
- Shicheng Zhang
(University of North Carolina at Chapel Hill School of Medicine)
- Yongfeng Liu
(University of North Carolina at Chapel Hill School of Medicine)
- Kuglae Kim
(University of North Carolina at Chapel Hill School of Medicine)
- Joel Karpiak
(University of California San Francisco, School of Medicine)
- Lily Y. Jan
(University of California, San Francisco
Howard Hughes Medical Institute)
- Soman N. Abraham
(Duke University Medical Center
Duke–National University of Singapore)
- Jian Jin
(Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)
- Brian K. Shoichet
(University of California San Francisco, School of Medicine)
- Jonathan F. Fay
(University of North Carolina at Chapel Hill School of Medicine)
- Bryan L. Roth
(University of North Carolina at Chapel Hill School of Medicine)
Abstract
The MRGPRX family of receptors (MRGPRX1–4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently1. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions2–5. MRGPRX2 couples to both Gi and Gq in mast cells6. Here we describe agonist-stabilized structures of MRGPRX2 coupled to Gi1 and Gq in ternary complexes with the endogenous peptide cortistatin-14 and with a synthetic agonist probe, respectively, and the development of potent antagonist probes for MRGPRX2. We also describe a specific MRGPRX4 agonist and the structure of this agonist in a complex with MRGPRX4 and Gq. Together, these findings should accelerate the structure-guided discovery of therapeutic agents for pain, itch and mast cell-mediated hypersensitivity.
Suggested Citation
Can Cao & Hye Jin Kang & Isha Singh & He Chen & Chengwei Zhang & Wenlei Ye & Byron W. Hayes & Jing Liu & Ryan H. Gumpper & Brian J. Bender & Samuel T. Slocum & Brian E. Krumm & Katherine Lansu & John , 2021.
"Structure, function and pharmacology of human itch GPCRs,"
Nature, Nature, vol. 600(7887), pages 170-175, December.
Handle:
RePEc:nat:nature:v:600:y:2021:i:7887:d:10.1038_s41586-021-04126-6
DOI: 10.1038/s41586-021-04126-6
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Citations
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Cited by:
- Yang Yang & Hye Jin Kang & Ruogu Gao & Jingjing Wang & Gye Won Han & Jeffrey F. DiBerto & Lijie Wu & Jiahui Tong & Lu Qu & Yiran Wu & Ryan Pileski & Xuemei Li & Xuejun Cai Zhang & Suwen Zhao & Terry K, 2023.
"Structural insights into the human niacin receptor HCA2-Gi signalling complex,"
Nature Communications, Nature, vol. 14(1), pages 1-11, December.
- Edin Muratspahić & Kristine Deibler & Jianming Han & Nataša Tomašević & Kirtikumar B. Jadhav & Aina-Leonor Olivé-Marti & Nadine Hochrainer & Roland Hellinger & Johannes Koehbach & Jonathan F. Fay & Mo, 2023.
"Design and structural validation of peptide–drug conjugate ligands of the kappa-opioid receptor,"
Nature Communications, Nature, vol. 14(1), pages 1-17, December.
- Lulu Guo & Yumu Zhang & Guoxing Fang & Lu Tie & Yuming Zhuang & Chenyang Xue & Qi Liu & Minghui Zhang & Kongkai Zhu & Chongzhao You & Peiyu Xu & Qingning Yuan & Chao Zhang & Lei Liu & Naikang Rong & S, 2023.
"Ligand recognition and G protein coupling of the human itch receptor MRGPRX1,"
Nature Communications, Nature, vol. 14(1), pages 1-12, December.
- Yunxuan Lei & Xin Guo & Yanping Luo & Xiaoyin Niu & Yebin Xi & Lianbo Xiao & Dongyi He & Yanqin Bian & Yong Zhang & Li Wang & Xiaochun Peng & Zhaojun Wang & Guangjie Chen, 2024.
"Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis,"
Nature Communications, Nature, vol. 15(1), pages 1-14, December.
- Aika Iwama & Ryoji Kise & Hiroaki Akasaka & Fumiya K. Sano & Hidetaka S. Oshima & Asuka Inoue & Wataru Shihoya & Osamu Nureki, 2024.
"Structure and dynamics of the pyroglutamylated RF-amide peptide QRFP receptor GPR103,"
Nature Communications, Nature, vol. 15(1), pages 1-13, December.
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