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Transmembrane peptide 4 and 5 of APJ are essential for its heterodimerization with OX1R
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Wan, Lei, Xu, Fangfang, Liu, Chang, Ji, Bingyuan, Zhang, Rumin, Wang, Peixiang, Wu, Fei, Pan, Yanyou, Yang, Chunqing, Wang, Chunmei and Chen, Jing (2020) Transmembrane peptide 4 and 5 of APJ are essential for its heterodimerization with OX1R. Biochemical and Biophysical Research Communications, 521 (2). pp. 408-413. doi:10.1016/j.bbrc.2019.10.146
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WRAP-Transmembrane-peptide-essential-heterodimerization-Chen-2019.pdf - Accepted Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (946Kb) | Preview |
Official URL: https://doi.org/10.1016/j.bbrc.2019.10.146
Abstract
Increasing evidence indicates some G protein-coupled receptors function as a heterodimer, which provide a novel target for therapeutics investigation. However, study on the receptor-receptor interaction interface, a potent target on interfering dimer formation, are still limited. Here, using bioluminescence resonance energy transfer (BRET) combined with co-immunoprecipitation (Co-IP), we found a new constitutive GPCR heterodimer, apelin receptor (APJ)-orexin receptor type 1 (OX1R). Both APJ and OX1R co-internalized when constantly subjected to cognate agonist (apelin-13 or orexin-A) specific to either protomer. Combined with BRET and immunostaining, the in vitro synthesized transmembrane peptides (TMs) interfering experiments suggests that TM4 and 5 of APJ act as the interaction interface of the APJ-OX1R heterodimer, and co-internalization could be disrupted by these peptides as well. Our study not only provide new evidence on GPCR heterodimerization, but address a novel heterodimerization interface, which can be severed as a potential pharmacological target.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology | |||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Peptides, G proteins -- Receptors -- Research, Orexins, Bioluminescence, Membrane proteins -- Research | |||||||||
| Journal or Publication Title: | Biochemical and Biophysical Research Communications | |||||||||
| Publisher: | Elsevier | |||||||||
| ISSN: | 0006-291X | |||||||||
| Official Date: | 8 January 2020 | |||||||||
| Dates: |
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| Volume: | 521 | |||||||||
| Number: | 2 | |||||||||
| Page Range: | pp. 408-413 | |||||||||
| DOI: | 10.1016/j.bbrc.2019.10.146 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||
| RIOXX Funder/Project Grant: |
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