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J. Biol. Chem., Vol. 279, Issue 52, 54002-54007, December 24, 2004
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From the
Westmead Millenium Institute, Westmead, New South Wales, Australia 2145 and the Rheumatology Department, Westmead Hospital, Westmead, New South Wales, Australia 2145
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.
Received for publication, April 8, 2004 , and in revised form, October 8, 2004.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Rheumatology Dept., Westmead Hospital, Westmead, NSW, Australia 2145. Tel.: 612-98458099; Fax: 612-98458317; E-mail: nickm{at}westgate.wh.usyd.edu.au.
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