A Conserved Basic Motif Mediates Membrane Anchoring and TRAF2 Recruitment Across Costimulatory TNFRs

ABSTRACT: Costimulatory receptors of the TNFR superfamily are key components in synthetic immunoreceptors, yet how their intracellular domains coordinate membrane anchoring with adaptor recruitment remains unresolved. Here, using solution-state NMR and membrane-reconstituted FRET assays, we identify a conserved basic-residue-rich sequence (BRS) in the juxtamembrane region of OX40 that binds anionic phospholipids and adopts a membrane-inserted conformation. This membrane engagement enables a dual-site interaction with TRAF2, combining canonical PxQxx binding with a secondary membrane-proximal interface, to promote robust NF-B activation. Disruption of the BRS impairs adaptor docking without reducing receptor surface expression or ligand-induced clustering. This regulatory architecture is further sup

SUBMITTER: Jiali Zhu 

PROVIDER: S-SCDT-10_1038-S44318-026-00868-Z | biostudies-other |

REPOSITORIES: biostudies-other