title: The topology, in model membranes, of the core peptide derived from the T-cell receptor transmembrane domain.
abstract: 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.
authors.affiliation: Department of Chemical Physics, Weizmann Institute of Science, 234 Hertzl St, Rehovot, 7632700 (Israel).
authors.forename: Erez
authors.initials: E
authors.lastname: Matalon
authors.forename: Omri
authors.initials: O
authors.lastname: Faingold
authors.forename: Miriam
authors.initials: M
authors.lastname: Eisenstein
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
authors.forename: Daniella
authors.initials: D
authors.lastname: Goldfarb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D004578:Electron Spin Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013113:Spin Labels
chemical_list: D017252:CD3 Complex; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013113:Spin Labels
keywords: DEER; EPR spectroscopy; ESEEM; core peptide; membrane proteins