Conformational Dynamics of β2-Microglobulin Analyzed by Reduction and Reoxidation of the Disulfide Bond

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Although native β2-microglobulin (β2-m), the light chain of the major histocompatibility complex class I antigen, assumes an immunoglobulin domain fold, it is also found as a major component of dialysis-related amyloid fibrils. In the amyloid fibrils, the conformation of β2-m is considered to be largely different from that of the native state, and a monomeric denatured form is likely to be a precursor to the amyloid fibril. To obtain insight into the conformational dynamics of β2-m leading to the for-mation of amyloid fibrils, we studied the reduction and reoxidation of the disulfide bond by reduced and oxidized dithiothreitol, respectively, and the effects on the reduction of the chaperonin GroEL, a model protein that might destabilize the native state of β2-m. We show that β2-m occasionally unfolds into a denatured form even under physiological conditions and that this transition is promoted upon interaction with GroEL. The results imply that in vivo interactions of β2-m with other proteins or membrane components could destabilize its native structure, thus stabilizing the amyloid precursor.
社団法人日本生化学会の論文