Spatial requirements for ITAM signaling in an intracellular natural killer cell model membrane.

ABSTRACT: FcγRIIIa-FcεRIγ complexes, upon stimulation by antibodies, cluster to initiate intracellular signaling and activate natural killer (NK) cells. Intracellular signaling involves Lck phosphorylation of ITAMs of each monomer of a FcεRIγ homodimer in a FcγRIIIa-FcεRIγ complex and subsequent binding of two phosphotyrosines (pY) in tandem by a Syk family kinase. However, how FcR clustering triggers ITAM signaling is not resolved. Molecular modeling and dynamics (MD) simulations are applied to generate ensembles of structures of the FcγRIIIa and FcεRIγ homodimeric cytoplasmic tails of FcγRIIIa-FcεRIγ complexes based on the transmembrane helices and cytoplasmic tails spaced 120, 80, and 50 Å apart to model different extents of clustering. Site-identification by ligand competitive saturation method

SUBMITTER: Chong G 

PROVIDER: S-EPMC9420803 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature