Pressure titration of the monomeric variant of transthyretin

Abstract

Transthyretin (TTR) is an indispensable transporter protein of thyroxine and a retinol molecule in humans. TTR has a stable homo-tetrameric structure in its native state, while upon dissociation into monomers, it becomes aggregation-prone and can form an amyloid fibril. Although the amyloidogenic propensity of TTR has been known and investigated since the late 1990s, the structural information regarding TTR’s amyloidogenic species is still elusive. Here, we employed high-pressure nuclear magnetic resonance (HP-NMR) approaches on the monomeric variant of TTR (TTR[F87M/L110M]; M-TTR) and observed that it experiences a two-step transition in response to the pressurized condition. Our study demonstrated that M-TTR in an ambient condition has heterogeneous structural features, which is likely related to the amyloidogenic propensity of TTR.