Structural basis for GSDMB pore formation and its targeting by IpaH7.8.

ABSTRACT: Gasdermins (GSDMs) are pore-forming proteins that play critical roles in host defence through pyroptosis^1,2. Among GSDMs, GSDMB is unique owing to its distinct lipid-binding profile and a lack of consensus on its pyroptotic potential^3-7. Recently, GSDMB was shown to exhibit direct bactericidal activity through its pore-forming activity⁴. Shigella, an intracellular, human-adapted enteropathogen, evades this GSDMB-mediated host defence by secreting IpaH7.8, a virulence effector that triggers ubiquitination-dependent proteasomal degradation of GSDMB⁴. Here, we report the cryogenic electron microscopy structures of human GSDMB in complex with Shigella IpaH7.8 and the GSDMB pore. The structure of the GSDMB-IpaH7.8 complex identifies a motif of three n

SUBMITTER: Wang C 

PROVIDER: S-EPMC10115629 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature