A histidine switch regulates pH-dependent filament formation by the caspase-9 CARD.

ABSTRACT: The caspase activation and recruitment domain (CARD) mediates protein-protein interactions in apoptotic and inflammatory signaling pathways. In humans, more than 30 proteins contain a CARD, several of which have been reported to polymerize into helical filaments. Here we found that the CARD from the apoptotic protease caspase-9 (C9^CARD) self assembles into filaments in vitro at physiological pH and salt concentrations. The C9^CARD more readily polymerizes under low-salt or mildly acidic conditions, suggesting a significant role for electrostatic interactions in mediating filament formation. Using NMR spectroscopy, we determined the pK _a of the lone histidine residue, H38, which supports a role for histidine protonation in enhancing filament for

SUBMITTER: Rawal S 

PROVIDER: S-EPMC12157618 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature