Structural basis for ACT1 oligomerization induced by IL-17 receptor hetero-tetramer.

ABSTRACT: The IL-17 receptors (IL-17Rs) play critical roles in immunity and inflammatory diseases. IL-17-induced heteromeric complexes between IL-17RA and another IL-17R trigger signaling by binding the downstream transducer ACT1 through interactions between their intracellular SEF/IL-17R (SEFIR) domains. The molecular mechanism of this process remains unclear. Here we present the cryo-EM structure of the complex of IL-17RA, IL-17RB and ACT1, showing that the IL-17RA and IL-17RB SEFIR domains form an asymmetric hetero-tetramer. The two IL-17RA SEFIR domains serve as the base to recruit ACT1, while IL-17RB stabilizes the IL-17RA dimer but makes no interaction with ACT1. IL-17RB, IL-17RA, and multiple ACT1 together form a double-stranded helical assembly. The C-terminal SEFIR extension (SEFEX) of IL-1

SUBMITTER: Zhang H 

PROVIDER: S-EPMC12828022 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature