title: Structure induction of the T-cell receptor zeta-chain upon lipid binding investigated by NMR spectroscopy.
abstract: The conformation of the cytoplasmic part of the zeta-chain of the T-cell receptor (TCR) in its free form and bound to detergent micelles has been investigated by heteronuclear NMR spectroscopy. The zeta-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 zeta-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 zeta-chain and to the zeta-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 zeta-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 zeta-chain is indeed intrinsically unstructured. Regions around the ITAM2 and ITAM3 sequences are involved in a highly dynamic binding of the free zeta-chain to a detergent micelle formed by the acidic lipid LMPG.
authors.affiliation: Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, Johann Wolfgang Goethe University Frankfurt, 60439 Frankfurt, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Duchardt
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Sigalov
authors.forename: Dikran
authors.initials: D
authors.lastname: Aivazian
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Stern
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
mesh_terms: D000595:Amino Acid Sequence; D008024:Ligands; D008823:Micelles; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*
chemical_list: D008024:Ligands; D008823:Micelles; D011948:Receptors, Antigen, T-Cell