Mechanism of GPR84 allosteric modulation at a helix 8-proximate site
-biased profile sustains macrophage phagocytosis of cancer cells without the desensitization induced by balanced agonists. Sequence analysis suggests that helix 8-proximate allosteric sites may be broadly targetable across class A GPCRs, while receptor-specific contacts enable selective modulation. These findings establish structural and mechanistic principles for biased allosteric modulation applicable beyond GPR84.
Authors
- Jingkai Zhou (ORCID: https://orcid.org/0000-0002-9867-3486)
- Andhika Bintang Mahardhika (ORCID: https://orcid.org/0000-0002-0456-1353)
- Laura Jenkins (ORCID: https://orcid.org/0000-0003-1382-8547)
- Angela J. Russell (ORCID: https://orcid.org/0000-0003-3610-9369)
- Irina G. Tikhonova (ORCID: https://orcid.org/0000-0002-6228-9431)
- Mingye Feng (ORCID: https://orcid.org/0000-0002-4960-4791)
- P Wang
- Zobaer Al Mahmud (ORCID: https://orcid.org/0000-0003-4048-927X)
- Fabian Gossen
- Abdul-Akim Guseinov
- Xuan Zhang
- Christa E Muller
- Cheng Zhang
- Yueming Li
- Graeme Milligan
Institutions
- Queen's University Belfast (GB)
- Mansfield University (US)
- University of Bonn (DE)
- University of Pittsburgh (US)
- Oxford Research Group (GB)
- University of Oxford (GB)
- City of Hope (US)
- Beckman Research Institute
- University of Glasgow (GB)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-12
- DOI
- https://doi.org/10.64898/2026.04.10.715585
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Pittsburgh
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Directorate for Biological Sciences
- Engineering and Physical Sciences Research Council