Structural Conservation and Effects of Alterations in T Cell Receptor Transmembrane Interfaces

Abstract

T cell receptors (TCRs) are octameric assemblies of type-I membrane proteins in which a receptor heterodimer (αβ δγ or pre-Tαβ) is associated with three dimeric signaling modules (CD3δε CD3γε and ζζ) at the T cell or pre-T cell surface. In the human αβTCR, the α and β transmembrane (TM) domains form a specific structure that acts as a hub for assembly with the signaling modules inside the lipid bilayer. Conservation of key polar contacts across the C-terminal half of this TM interface suggests that the structure is a common feature of all TCR types. In this study, using molecular dynamics simulations in explicit lipid bilayers, we show that human δγ and pre-Tαβ TM domains also adopt stable α..