title: Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.
abstract: Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.
authors: Basic Research Laboratories, Toray Industries, Inc. Kanagawa, Japan.
authors: J
authors: J
authors: Utsumi
authors: S
authors: S
authors: Yamazaki
authors: K
authors: K
authors: Kawaguchi
authors: S
authors: S
authors: Kimura
authors: H
authors: H
authors: Shimizu
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003902:Detergents; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000648:ultrastructure*; D011108:Polymers; D011487:Protein Conformation; D011489:Protein Denaturation; D013329:Structure-Activity Relationship
chemical_list: D003902:Detergents; D007370:Interferon Type I; D011108:Polymers