Paper BI-ThP10
Membrane Binding and Structure for Cytoplasmic Domain of Zeta Subunit of T Cell Receptor

Thursday, November 3, 2011, 6:00 pm, Room East Exhibit Hall

The cytoplasmic domain of the T-cell receptor zeta subunit, ζ_cyt, a cell surface protein complex responsible for binding peptide fragments of foreign antigens bound to major histocompatibility complex (MHC) proteins, is sufficient to couple receptor ligation to intracellular signaling cascades [1]. These domains carry immunoreceptor tyrosine-based activation motifs (ITAMs), i.e. signaling motifs that are phosphorylated by tyrosine kinases following receptor crosslinking. The phosphorylation of ITAMs is a first and obligatory step in signal transduction. ζ_cyt has been shown to be unstructured in aqueous solution and to assume a helical conformation in the presence of anionic lipid vesicles [2,3]. Membrane binding and membrane-induced conformational changes likely plays an important role in signal transduction, but no direct structural information on these functionally important lipid-bound states was available so far. Using a synthetic membrane model, i.e., fluid lipid bilayers tethered to planar solid supports [4,5], we report surface plasmon resonance (SPR) results on the binding kinetics and neutron reflectivity investigations of the association of the disordered ζ_cyt with membranes. We determine the extent to which the protein penetrates into the bilayer and discuss structural details of the ζ_cyt–lipid interaction.

1. M. E. Call, K. W. Wucherpfennig, Annu. Rev. Immunol. 23 (2005), 101-125.

2. A. Sigalov, Semin. Immunol. 17 (2005), 51-64.

3. D. Aivazian, L. J. Stern, Nat. Struc. Biol. 7 (2000), 1023-1026.

4. D. J. McGillivray, et al., Biointerphases 2 (2007), 21-33.