The residual structure of acid-denatured β -microglobulin is relevant to an ordered fibril morphology.

β -Microglobulin (β2m) forms amyloid fibrils in vitro under acidic conditions. Under these conditions, the residual structure of acid-denatured β2m is relevant to seeding and fibril extension processes. Disulfide (SS) bond-oxidized β2m has been shown to form rigid, ordered fibrils, whereas SS bond-reduced β2m forms curvy, less-ordered fibrils.

Enhanced accessibility and hydrophobicity of amyloidogenic intermediates of the β2-microglobulin D76N mutant revealed by high-pressure experiments.

β2-Microglobulin (β2m) is the causative protein of dialysis-related amyloidosis. Its unfolding mainly proceeds along the pathway of N →U ⇄ U, whereas refolding follows the U → I (→N) →N pathway, in which N, I, and U are the native, intermediate, and unfolded states, respectively, with the Pro32 peptidyl-prolyl bond in cis or trans conformation as indicated by the subscript. It is noted that the I state is a putative amyloidogenic precursor state.

Loosening of Side-Chain Packing Associated with Perturbations in Peripheral Dynamics Induced by the D76N Mutation of β-Microglobulin Revealed by Pressure-NMR and Molecular Dynamic Simulations.

β-Microglobulin (βm) is the causative protein of dialysis-related amyloidosis, and its D76N variant is less stable and more prone to aggregation. Since their crystal structures are indistinguishable from each other, enhanced amyloidogenicity induced by the mutation may be attributed to changes in the structural dynamics of the molecule. We examined pressure and mutation effects on the βm molecule by NMR and MD simulations, and found that the mutation induced the loosening of the inter-sheet packing of βm, which is relevant to destabilization and subsequent amyloidogenicity.