The Stalk Domain of NKp30 Contributes to Ligand Binding and Signaling of a Preassembled NKp30-CD3? Complex.

ABSTRACT: The natural cytotoxicity receptor (NCR) NKp30 (CD337) is a key player for NK cell immunosurveillance of infections and cancer. The molecular details of ligand recognition and its connection to CD3? signaling remain unsolved. Here, we show that the stalk domain (129KEHPQLGAGTVLLLR143) of NKp30 is very sensitive to sequence alterations, as mutations lead to impaired ligand binding and/or signaling capacity. Surprisingly, the stalk domains of NKp30 and NKp46, another NCR employing CD3? for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting, and/or ligand-induced receptor signaling. Further mutational studies, N-glycosylation mapping, and plasma membrane targeting studies in the absence and presence of CD3? suggest two interconvertible types of NCR-CD3? assemblies: 1) a signaling incompetent structural NKp30-CD3? complex and 2) a ligand-induced signaling competent NKp30-CD3? complex. Moreover, we propose that ligand binding triggers translocation of Arg-143 from the membrane interface into the membrane to enable alignment with oppositely charged aspartate residues within CD3? and activation of CD3?-signaling.

SUBMITTER: Memmer S 

PROVIDER: S-EPMC5207244 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature