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Journal/Book: ChemBioChem
Published: 2007
Pages: 820–827
Volume: 8
Issue:
Accession no.: 126
Publisher:
ISBN:

Structure induction of the T-cell receptor zeta-chain upon lipid binding investigated by NMR spectroscopy.

Elke Duchardt, Alexander B Sigalov, Dikran Aivazian, Lawrence J Stern, Harald Schwalbe
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.
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Prof. Dr. Harald Schwalbe
Institut für Organische Chemie und Chemische Biologie
Johann Wolfgang Goethe Universität
Max-von-Laue-Str. 7
D-60438 Frankfurt am Main
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