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Interferon‐inducible large GTPases are critical for innate immunity. The distinctive feature of a large GTPase, human guanylate binding protein‐1 (hGBP1), is the sequential hydrolysis of GTP into GMP via GDP. Despite several structural and biochemical studies, the underlying mechanism of assembly‐stimulated GMP formation by hGBP1 and its role in immunity are not fully clarified. Using a series of...