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In this issue of Cell, two papers report agonist-bound cryo-EM structures of the cannabinoid receptor, CB2, in complex with Gi. Importantly, beyond providing information that could help distinguish CB2 ligand binding from CB1, these structures support the existence of a nucleotide-free state during G-protein signaling. We have developed a platform for quantitative genetic interaction mapping using viral infectivity as a functional readout and constructed a viral host-dependency epistasis map (vE-MAP) of 356 human genes linked to HIV funct