A peptide derived from LFA-1 protein that modulates T-cell adhesion binds to soluble ICAM-1 protein.
Leukocyte function associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) have been shown to be critical for adhesion process and immune response. Modulation or inhibition of the interaction between LFA-1/ICAM-1 interactions can result in therapeutic effects. Our group and others have shown that peptides derived from ICAM-1 or LFA-1 inhibit adhesion in a homotypic T-cell adhesion assay. It is likely that the peptides derived from ICAM-1 bind to LFA-1 and peptides derived from LFA-1 bind to ICAM-1 and inhibit the adhesion interaction. However, there are no concrete experimental evidence to show that peptides bind to either LFA-1 or ICAM-1 and inhibit the adhesion. Using NMR, CD and docking studies we have shown that an LFA-1 derived peptide binds to soluble ICAM-1. Docking studies using "autodock" resulted in LFA-1 peptide interacting with the ICAM-1 protein near Glu34. The proposed model based on our experimental data indicated that the LFA-1 peptide interacts with the protein via three intermolecular hydrogen bonds. Hydrophobic interactions also play a role in stabilizing the complex.
Jois
Seetharama D S
SD
Department of Pharmacy, 18 Science Drive 4, National University of Singapore, Singapore 117543, Singapore. phasdsj@nus.edu.sg
Teruna
Teruna J
TJ
D002448:Cell Adhesion; D002942:Circular Dichroism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology
D016169:Lymphocyte Function-Associated Antigen-1; D010456:Peptides, Cyclic; C480762:cyclo(1,12)Phen(1)Asp(2)Leu(3)Ser(4)Tyr(5)Ser(6)Leu(7)Asp(8)Asp(9)Leu(10)Arg(11)Cys(12); D018799:Intercellular Adhesion Molecule-1