Atomic mechanisms of full-length ASC-mediated inflammasome assembly.

ABSTRACT: ASC (Apoptosis-associated Speck-like protein containing a CARD) is a key adaptor protein that assembles inflammasomes by linking sensors such as NLRP3 to effectors like Caspase-1 via its PYD and CARD Death Domains. Due to ASC's propensity to self-aggregate, most high-resolution structural studies focused on isolated PYD or CARD domains, leaving the atomic basis of full-length ASC assembly unknown. Here we determine atomic-resolution cryo-EM structures of PYD and CARD filaments from full-length ASC, revealing characteristic multitrack bundles composed of alternating ASC^PYD and ASC^CARD filaments that expose multiple interfaces for flexible assembly and efficient signaling. We further show that Caspase-1 filaments nucleate specifically from the B-end of ASC^CARD

SUBMITTER: Xue D 

PROVIDER: S-EPMC12658066 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature