THE CRYSTAL-STRUCTURE OF TRANSTHYRETIN FROM CHICKEN

The crystal structure of chicken transthyretin has been solved at 290- pm resolution by molecular-replacement techniques. Transthyretin is th e protein component of the amyloid fibrils found in patients suffering from either familial amyloidotic polyneuropathy or senile systemic am yloidosis. Familial amyloidotic polyneuropathy is an autosomal dominan t hereditary type of amyloidosis which involves transthyretin with eit her one or two amino acid substitutions. The three-dimensional structu re of chicken transthyretin was determined in order to compare a non-a myloidogenic, species-variant transthyretin with wild-type and mutant transthyretin molecules. Of the 31 chicken-to-human residue difference s, 9 occur at positions which in human transthyretin give rise to amyl oidogenic variants although none corresponds to the appropriate side-c hain substitutions. The model of chicken transthyretin has been refine d to an R-factor of 19.9%. The overall fold of the protein is that of an all-beta protein. Compared with wild-type human transthyretin the a vian transthyretin shows quite large differences in the region known t o be involved in binding to retinol-binding protein, it has a much sho rter helical component than the human protein and some of the monomer- monomer interactions are different.