The Crystal Structure of Transthyretin from Chicken

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Abstract
The crystal structure of chicken transthyretin has been solved at 290‐pm resolution by molecular‐replacement techniques. Transthyretin is the protein component of the amyloid fibrils found in patients suffering from either familial amyloidotic polyneuropathy or senile systemic amyloidosis. Familial amyloidotic polyneuropathy is an autosomal dominant hereditary type of amyloidosis which involves transthyretin with either one or two amino acid substitutions. The three‐dimensional structure of chicken transthyretin was determined in order to compare a non‐amyloidogenic, species‐variant transthyretin with wild‐type and mutant transthyretin molecules. Of the 31 chicken‐to‐human residue differences, 9 occur at positions which in human transthyretin give rise to amyloidogenic variants although none corresponds to the appropriate side‐chain substitutions. The model of chicken transthyretin has been refined to an R ‐factor of 19.9%. The overall fold of the protein is that of an all‐β protein. Compared with wild‐type human transthyretin the avian transthyretin shows quite large differences in the region known to be involved in binding to retinol‐binding protein, it has a much shorter helical component than the human protein and some of the monomer‐monomer interactions are different.