Scheme 1. Mechanism of TTR Disassembly and Reassembly Highlighting the Role of Water Molecules in the Process.

When “cold” water molecules (dark blue spheres) that form the tetramer interface are disrupted, tetramers disassemble into dimers and monomers. During reassembly, interactions between the complex and water molecules re-form; however, it must be noted that the water network of the new tetramer may not be the same as the original water network.