Figure 1.

Propensities of steric zipper formation of each 6‐residue segment within the TTR sequence. Amyloidogenic propensities were calculated using the 3D profiling method ZipperDB.15 Segments having energies of −23 kcal mol − 1 (green dashed line) or lower are predicted to form fibrils.16 Segments that we selected for crystallization are represented with red bars. The segment containing the familial mutation ATTR‐D38A is represented with a blue bar. The ZipperDB Rosetta energy prediction of the wild‐type sequence ³⁷ADDTWE⁴² is −18.0 kcal mol⁻¹ compared to −20.0 kcal mol⁻¹ of the mutant sequence ³⁷AADTWE⁴². The schematic of the secondary structure of native TTR is shown on top of the sequence. The blue and pink boxes highlight the TTR segment sequences of the N‐terminal and C‐terminal regions, respectively, that we described in this study. Only two segments of the N‐terminus, 28VAVHVF³³ and ³⁷AADTWE⁴², resulted in the formation of diffracting crystals. From the C‐terminus, only the segment ⁶⁵VEGIYK⁷⁰ did not result in a crystal structure.