Analysis of the Human Interleukin-6/Human Interleukin-6 Receptor Binding Interface at the Amino Acid Level: Proposed Mechanism of Interaction

摘要: The interaction between interleukin-6 (IL-6) and IL-6 receptor (IL-6R) is the initial most specific step in signaling pathway. Understanding its mechanism at amino acid level basis for developing small IL-6-inhibiting molecules. We studied human (hIL-6)/hIL-6R binding interface by a combination of molecular modelling site-directed mutagenesis. Our model suggests that center two molecules consists hydrophobic contacts predicted to account binding-free energy. These can be regarded as core shielded hydrophilic residues are also needed recognition. Following this hypothesis, we altered hIL-6 hIL-6R reside contact region interact with each other. capacity these mutants form an IL-6/IL-6R complex their ability transduce signal. This combined approach has led identification certain residue-clusters rational explanation interactions, suggesting therein likely formation. results confirm predictive strongly support our hypothesis. Comparison other cytokines alpha-subunit receptors structural location sites conserved.