T cell antigen receptor peptide-lipid membrane interactions using surface plasmon resonance.
This study examines the binding properties of a new class of immunomodulating peptides derived from the transmembrane region of the T cell antigen receptor, on model membranes using surface plasmon resonance. The di-basic "core" peptide was found to bind to both zwitterionic and anionic model membranes as well as to a T cell membrane preparation. By contrast, switching one or both of the basic residues to acidic residues led to a complete loss of binding to model membranes. In addition, the position of the charged amino acids in the sequence, the number of hydrophobic amino acids between the charged residues, and substitution of one or both basic to neutral amino acids were found to effect binding. These results when compared with in vitro T cell stimulation assays and in vivo adjuvant-induced arthritis models, showed very close correlation and confirmed the findings that amino acid charge and location may have a role in peptide activity. These initial biophysical peptide-membrane interactions are critically important and correlate well with the subsequent cellular expression and biological effect of these hydrophobic peptides. Targeting and understanding the biophysical interactions between peptides and membranes at their site of action is paramount to the description of cell function and drug design.
Westmead Millenium Institute, Westmead, New South Wales, Australia 2145.
Veronika
V
Bender
Marina
M
Ali
Michael
M
Amon
Eve
E
Diefenbach
Nicholas
N
Manolios
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004563:Electrochemistry; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000648:ultrastructure*
D008081:Liposomes; D008563:Membrane Lipids; D008565:Membrane Proteins; D010455:Peptides; D010715:Phosphatidylglycerols; D011948:Receptors, Antigen, T-Cell; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine