Structural and dynamic mechanisms of cannabinoid receptors
Xiucheng Guo1, Fahui Li2, Feng Zhang1
1The Second Affiliated Hospital, and School of Clinical and Basic Medical Sciences of Shandong First Medical University& Shandong Academy of Medical Sciences, Taian, Shandong 271000, China.
None:
Cannabinoids and their G protein-coupled receptors (GPCRs) within the endocannabinoidome are pivotal regulators of neuromodulation, inflammation, and metabolic homeostasis. Dysregulation of this system has been associated with a wide spectrum of pathological conditions, including neuropsychiatric disorders, chronic pain, and immune dysfunction. In this review, we summarize recent structural advances in cannabinoid receptors that have deepened our understanding of receptor activation, allosteric modulation, transducer coupling selectivity, and dynamic conformational mechanisms. These structural insights will facilitate cannabinoid receptor-targeted drug discovery, enabling the development of therapeutics with improved subtype selectivity, enhanced signaling precision, and reduced off-target effects.
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