Structural and functional heterogeneity of the amino-terminal receptor-binding domain of human interferon-alpha 2

Structural immunoanalysis of human interferon (IFN)-alpha 2c revealed antig enic and functional heterogeneity in its N-terminal receptor-binding domain (loop AB). Monoclonal antibodies (mAbs) mapped to the region 30-53 of IFN- alpha 2 defined three partially overlapping antigenic sites designated here as 'a', 'b' and 'c'. For the high-affinity binding of IFN-alpha 2c to the cellular receptor, site b located in segment 34-41 and site c (residues 43- 53) appeared to be most important. Only the part of site a (amino acids 30- 33) seemed to be involved in the interaction with receptor. The segment of residues 30-46 forms a relatively straight structure on the protein surface , according to the three-dimensional model of human IFN-alpha 2. (C) 1999 E lsevier Science B.V. All rights reserved.