Solution structure of a peptide derived from the β subunit of LFA-1

Abstract

Cell-adhesion molecules are critical for immune response. It is well known that the inhibition of adhesion is very effective in immunotherapy and that the peptides derived from leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1) modulate cell-adhesion interaction. The three-dimensional structure of a cyclic peptide, Cyclo(1,12)Pen 1-Asp2-Leu3-Ser4-Tyr 5-Ser6-Leu7-Asp8-Asp 9-Leu10-Arg11-Cys12 (cLBEL) derived from the β subunit of LFA-1 which is known to modulate homotypic T-cell-adhesion process has been studied using NMR, CD and molecular dynamics (MD) simulation. The peptide exhibits two possible conformations in solution. Structure I has a conformation with two consecutive β-turns involving residues Tyr5-Ser6-Leu7-Asp8 and Asp9-Leu10-Arg11-Cys12. Structure II has a β-turn at Tyr5-Ser6-Leu7-Asp 8 and forms a β-hairpin type of conformation. © 2003 Elsevier Inc. All rights reserved.