An evolution-guided framework is proposed to accelerate the discovery and therapeutic targeting of understudied dark channels by integrating sequence, structure, and functional data from diverse organisms.
Biochemical and genetic evidence identifies ATP5I as a biguanide target, redefining biguanide action through ATP synthase regulation and assembly, mitochondrial architecture, and mitochondrial protein turnover.
Soenke Cordeiro, Robert Patejdl ... Marianne A Musinszki
Identification of mangostins as potent BK channel activators links natural xanthones to vascular smooth muscle relaxation, providing a mechanistic basis for their reported antihypertensive effects.
Resolving the mechanism of RXR ligand-dependent NR4A-RXR nuclear receptor heterodimer activation requires a diverse ligand set that includes heterodimer-selective agonists.
