A glimpse of a possible amyloidogenic intermediate of transthyretin

Studies have indicated that partially unfolded states occur under condition s that favor amyloid formation by transthyretin (TTR), as well as other amy loidogenic proteins. In this study, we used hydrogen exchange measurements to show that there is selective destabilization of one half of the beta-san dwich structure of TTR under such conditions. This provides more direct inf ormation about conformational fluctuations than previously available, and w ill facilitate design of future experiments to probe the intermediates crit ical to amyloid formation.