Structure Induction of the T‐Cell Receptor ζ‐Chain upon Lipid Binding Investigated by NMR Spectroscopy

Publisher Website
Google Scholar
Abstract
The conformation of the cytoplasmic part of the ζ‐chain of the T‐cell receptor (TCR) in its free form and bound to detergent micelles has been investigated by heteronuclear NMR spectroscopy. The ζ‐chain is considered to be a mediator between the extracellular antigen and the intracellular signal‐transduction cascade leading to T‐cell activation. Earlier studies suggested a T‐cell activation mechanism that involved a TCR‐state‐dependent lipid incorporation propensity of the ζ‐chain accompanied by a helical folding transition. In order to support this proposed mechanism, standard protein NMR assignment and secondary‐structure‐elucidation techniques have been applied to the free TCR ζ‐chain and to the ζ‐chain bound to the detergent LMPG, which forms a micelle, in order to obtain the structural characteristics of this folding transition in a residue‐resolved manner. We could assign the resonances of the free ζ‐chain at 278 K, and this formed the basis for chemical‐shift‐perturbation studies to identify lipid binding sites. Our NMR results show that the free TCR ζ‐chain is indeed intrinsically unstructured. Regions around the ITAM2 and ITAM3 sequences are involved in a highly dynamic binding of the free ζ‐chain to a detergent micelle formed by the acidic lipid LMPG.