These authors contributed equally to this work.
The Topology, in Model Membranes, of the Core Peptide Derived from the T-Cell Receptor Transmembrane Domain
Version of Record online: 24 JUL 2013
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 14, Issue 14, pages 1867–1875, September 23, 2013
How to Cite
Matalon, E., Faingold, O., Eisenstein, M., Shai, Y. and Goldfarb, D. (2013), The Topology, in Model Membranes, of the Core Peptide Derived from the T-Cell Receptor Transmembrane Domain. ChemBioChem, 14: 1867–1875. doi: 10.1002/cbic.201300191
- Issue online: 14 SEP 2013
- Version of Record online: 24 JUL 2013
- Manuscript Received: 28 MAR 2013
- Israel Science Foundation (ISF)
- core peptide;
- EPR spectroscopy;
- membrane proteins
The T-cell receptor–CD3 complex (TCR–CD3) serves a critical role in protecting organisms from infectious agents. The TCR is a heterodimer composed of α- and β-chains, which are responsible for antigen recognition. Within the transmembrane domain of the α-subunit, a region has been identified to be crucial for the assembly and function of the TCR. This region, termed core peptide (CP), consists of nine amino acids (GLRILLLKV), two of which are charged (lysine and arginine) and are crucial for the interaction with CD3. Earlier studies have shown that a synthetic peptide corresponding to the CP sequence can suppress the immune response in animal models of T-cell-mediated inflammation, by disrupting proper assembly of the TCR. As a step towards the understanding of the source of the CP activity, we focused on CP in egg phosphatidylcholine/cholesterol (9:1, mol/mol) model membranes and determined its secondary structure, oligomerization state, and orientation with respect to the membrane. To achieve this goal, 15-residue segments of TCRα, containing the CP, were synthesized and spin-labeled at different locations with a nitroxide derivative. Electron spin-echo envelope modulation spectroscopy was used to probe the position and orientation of the peptides within the membrane, and double electron–electron resonance measurements were used to probe its conformation and oligomerization state. We found that the peptide is predominantly helical in a membrane environment and tends to form oligomers (mostly dimers) that are parallel to the membrane plane.