Highlights d Biochemical and microscopic evidence indicates cGAS is a plasma membrane protein d The cGAS N terminus interacts with PI(4,5)P 2 to mediate membrane localization d Mislocalized cGAS mutants drive lethal interferon responses to genotoxic stress d Mislocalized cGAS mutants are poorly responsive to DNA virus infection

eThe Nipah virus phosphoprotein (P) is multimeric and tethers the viral polymerase to the nucleocapsid. We present the crystal structure of the multimerization domain of Nipah virus P: a long, parallel, tetrameric, coiled coil with a small, ␣-helical cap structure. Across the paramyxoviruses, these domains share little sequence identity yet are similar in length and structural organization, suggesting a common requirement for scaffolding or spatial organization of the functions of P in the virus life cycle.

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