T-cell antigen receptor (TCR) transmembrane peptides: A new paradigm for the treatment of autoimmune diseases.
Cell surface membranes are generally considered as inert and hydrophobic providing a stable physical barrier that anchor proteins and maintain cellular homeostasis between the intra- and the extra-cellular environment. The integral proteins that transverse membranes do so once or multiple times and can function alone or as part of a larger complex. Far from being inert, there is a multiplicity of biophysical factors that drive protein-protein and protein-lipid interactions within membranes that are being increasingly recognised as very important for cellular function. Unravelling these "hot-spots" on the contact surface of transmembrane (TM) proteins and targeting peptides to these sites to interrupt the cohesive interaction between the proteins provides both an enormous challenge and a huge therapeutic potential that as yet remains unrecognized. Indeed, with biopharmaceutical research on the rise, TM peptides may prove a useful innovation. Using the T-cell antigen receptor (TCR) as a model system of multi-subunits interacting at the TM via electrostatic charges the potential for peptides as therapeutic agents to interfere with normal immune responses is discussed. The principles of such can be extended to other similar receptor systems including those involved in cancer or infection.
Manolios
Nicholas
N
Department of Rheumatology, Westmead Hospital, Westmead, NSW, Australia. Nick_manolios@wmi.usyd.edu.au
Ali
Marina
M
Bender
Vera
V
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell