Structural and ICAM-1-docking properties of a cyclic peptide from the I-domain of LFA-1: an inhibitor of ICAM-1/LFA- 1-mediated T-cell adhesion

Journal of Biomolecular Structure & Dynamics
Christine R XuTeruna J Siahaan

Abstract

The purpose of this work was to study the conformation of cyclic peptide 1, cyclo(1,12)-Pen1-Ile2-Thr3-Asp4-Gly5-Glu6-Ala7- Thr8-Asp9-Ser10-Gly11-Cys12-OH, derived from the I-domain of the LFA-1 alpha-subunit. We found that cyclic peptide 1 can bind to the D1-domain of ICAM-1 and inhibit ICAM-1/LFA-1-mediated homotypic and heterotypic T-cell adhesion. To understand the bioactive conformation and binding requirements for cyclic peptide 1, its solution structure was studied using NMR, CD, and molecular dynamics simulations. Furthermore, possible binding properties between the cyclic peptide and the D1-domain of ICAM-1 were evaluated using docking experiments. This cyclic peptide has a stable betaII -turn at Asp4- Gly5-Glu6-Ala7 and a betaI-turn at Pen1-Ile2-Thr3-Asp4; a less stable betaV-turn is found at the C-terminal region. The beta-turn at Asp4- Gly5-Glu6-Ala7 was also found in the X-ray structure of the I-domain of LFA-1. Our CD studies showed that the peptide binds to calcium/magnesium and forms a 1:1 (peptide:calcium/magnesium) complex with low cation concentrations and multiple types of complexes with higher cation concentrations. Binding to divalent cations causes a conformational change in peptide 1; this is consistent ...Continue Reading

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Citations

Jun 23, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Ahmed H Badawi, Teruna J Siahaan
Aug 5, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Naoki KobayashiTeruna J Siahaan
Dec 9, 2008·Biochimica Et Biophysica Acta·Nicolas WeissPierre-Olivier Couraud
Aug 28, 2007·Chemical Biology & Drug Design·Helena Yusuf-MakagiansarTeruna J Siahaan
Aug 5, 2003·The Journal of Peptide Research : Official Journal of the American Peptide Society·L O SillerudR S Larson
Aug 21, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Meng HuangChristopher G Kevil

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Methods Mentioned

BETA
NMR
nuclear
circular

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