Processes underlying interactions of human lactoferrin with the Jurkat human lymphoblastic T-cell line receptor .1. Quantitative structure-affinity relationships studies

Human lactoferrin displays considerable structural homology with transferrins of other species. However, lactoferrins and transferrins play distinct biological roles and bind to specific cell receptors. Previous reports have shown that residues 4-52 of human lactoferrin are potentially involved in interaction with a specific T-lymphocyte receptor. In the present study, competitive binding assays of lactoferrin to the Jurkat human lymphoblastic T-cell line were performed using seven lactoferrins and transferrins, as well as both C-terminal lobes of human and bovine lactoferrins. Classical quantitative structure-affinity relationships (QSAR) models revealed important descriptors, namely H-bonds donor and acceptor groups of amino acid side chains, demonstrating that hydrogen bonding is a significant binding factor. This report points out the importance of residues R3, Q7, P14, N13, T17, F20, Q23, R24, K28, S38, D43, S44, P45, Q47, Q50 and N55 of human lactoferrin in the interaction with the lymphocyte receptor. The most important residues which contribute positively to the inhibition of the binding affinity are R3, Q7, Q23, R24, S38, the chemical groups involved in H-bonding are R3-(NH), Q7-(=O), Q23-(=O), R24-(NH), S38-(OH).