Restoration of Myoglobin Native Fold from Its Initial State of Amyloid Formation by Trehalose

• Published in: The journal of physical chemistry. B Vol. 122; no. 50; pp. 11962 - 11968
• Main Authors: Hirai, Mitsuhiro, Ajito, Satoshi, Iwase, Hiroki, Takata, Shin-ichi, Ohta, Noboru, Igarashi, Noriyuki, Shimizu, Nobutaka
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.12.2018
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/acs.jpcb.8b09379

Organisms having tolerances against extreme environments produce and accumulate stress proteins and/or sugars in cells against the extreme environment such as high or low temperature, drying, and so forth. Sugars and/or polyols are known to prevent protein denaturation and enzyme deactivation. In particular, trehalose has received considerable attention because of its association with cryptobiosis and anhydrobiosis. This study focuses on the restoration of acid-denatured amyloid transition of myoglobin by trehalose. Myoglobin is known to proceed amyloidogenic reaction under denaturation conditions. We found that acid-denatured myoglobin at an initial process of amyloidogenic reaction (helix-to-sheet transition followed by oligomerization) at 25 °C was substantially restored to its native structure by trehalose. This action was prominent during the early stage of amyloid formation. Recent results showed that sugars are preferentially excluded from the protein surface to preserve its hydration shell and stabilize the protein structure against chemical and thermal denaturation. Therefore, the present results suggest that trehalose will restore the tightly bound water molecules around the hotspot (G-helix) of myoglobin on the amyloid transition by its intrinsic preservative action of the native hydration shell against denaturation. The present finding on the restorative action by trehalose could provide new insights into protein folding and amyloidosis.