Jun 24, 2020 · Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic …

Jul 1, 2020 · The underlying molecular mechanism for hGBP1's diverse antimicrobial functions is unknown. Here, we demonstrate that hGBP1 binds directly to LPS and induces "detergent-like" LPS clustering through protein polymerization.

LPS-induced activation of non-canonical inflammasomes triggers pyroptotic cell death and cytokine release through cleavage of GasderminD (GSDMD), a latent pore forming protein, in a process critical for protection against cytosol-invading bacteria as well as the induction of endotoxin shock 7–10.

To activate pyroptosis, GBPs facilitate sensing of the gram-negative bacterial outer membrane component lipopolysaccharide (LPS) by the noncanonical caspase-4 inflammasome. There are seven human GBP paralogs, and it is unclear how each GBP contributes to LPS sensing and pyroptosis induction.

Apr 19, 2016 · Here we investigate the critical roles of interferon-induced GBPs in directing inflammasome subtype–specific responses and their consequences for cell-autonomous immunity to a wide variety of...

Oct 1, 2023 · Guanylate-binding proteins (GBPs) have newly identified functions, including pattern-recognition capabilities and pathogen-selective antimicrobial activities against bacteria, viruses, and parasites.

Aug 26, 2021 · LPS contamination of the cytosol elicits a caspase-dependent inflammasome pathway promoting cytokine release and host cell death. Here, we report an immune GTPase network controls multiple steps in this pathway by genome-engineering mice to lack 7 different guanylate-binding proteins (GBPs).

Jun 15, 2020 · Multiple antagonists of the pathway encoded by Shigella flexneri, a cytosol-adapted bacterium, provide compelling evolutionary evidence for the importance of the GBP–caspase-4 pathway in...

Two alternative modes for GBP-induced caspase-4 recruitment to membrane-embedded LPS have been proposed. A high molecular weight complex formed by GBP-LPS could promote the recruitment of caspase-4 and subsequently transfer LPS onto caspase-4 to trigger its activation.

GBPs promote caspase-4 (CASP4) activation by enhancing its interactions with lipopolysaccharide (LPS), a component of the outer envelope of Gram-negative bacteria. Once activated, CASP4 promotes the formation of noncanonical inflammasomes, signaling platforms that mediate pyroptosis.