title: Kinetic and conformational properties of a novel T-cell antigen receptor transmembrane peptide in model membranes.
abstract: Core peptide (CP; GLRILLLKV) is a 9-amino acid peptide derived from the transmembrane sequence of the T-cell antigen receptor (TCR) alpha-subunit. CP inhibits T-cell activation both in vitro and in vivo by disruption of the TCR at the membrane level. To elucidate CP interactions with lipids, surface plasmon resonance (SPR) and circular dichroism (CD) were used to examine CP binding and secondary structure in the presence of either the anionic dimyristoyl-L-alpha-phosphatidyl-DL-glycerol (DMPG), or the zwitterionic dimyristoyl-L-alpha-phoshatidyl choline (DMPC). Using lipid monolayers and bilayers, SPR experiments demonstrated that irreversible peptide-lipid binding required the hydrophobic interior provided by a membrane bilayer. The importance of electrostatic interactions between CP and phospholipids was highlighted on lipid monolayers as CP bound reversibly to anionic DMPG monolayers, with no detectable binding observed on neutral DMPC monolayers.CD revealed a dose-dependent conformational change of CP from a dominantly random coil structure to that of beta-structure as the concentration of lipid increased relative to CP. This occurred only in the presence of the anionic DMPG at a lipid : peptide molar ratio of 1.6:1 as no conformational change was observed when the zwitterionic DMPC was tested up to a lipid : peptide ratio of 8.4 : 1.
authors.affiliation: Rheumatology Department, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Amon
authors.forename: Marina
authors.initials: M
authors.lastname: Ali
authors.forename: Veronika
authors.initials: V
authors.lastname: Bender
authors.forename: Kristopher
authors.initials: K
authors.lastname: Hall
authors.forename: Marie-Isabel
authors.initials: MI
authors.lastname: Aguilar
authors.forename: Janice
authors.initials: J
authors.lastname: Aldrich-Wright
authors.forename: Nicholas
authors.initials: N
authors.lastname: Manolios
mesh_terms: D007700:Kinetics; D008567:Membranes, Artificial; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D008567:Membranes, Artificial; D010455:Peptides; D011948:Receptors, Antigen, T-Cell