Membrane-mediated regulation of the intrinsically disordered CD3ϵ cytoplasmic tail of the TCR.

ABSTRACT: The regulation of T-cell-mediated immune responses depends on the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) on T-cell receptors. Although many details of the signaling cascades are well understood, the initial mechanism and regulation of ITAM phosphorylation remains unknown. We used molecular dynamics simulations to study the influence of different compositions of lipid bilayers on the membrane association of the CD3ϵ cytoplasmic tails of the T-cell receptors. Our results show that binding of CD3ϵ to membranes is modulated by both the presence of negatively charged lipids and the lipid order of the membrane. Free-energy calculations reveal that the protein-membrane interaction is favored by the presence of nearby basic residues and the ITAM tyrosines. Phosp

SUBMITTER: Lopez CA 

PROVIDER: S-EPMC4457001 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature