A Comparison of the Proteins of Normal and Trichothiodystrophic Human Hair

A study has been made of the changes in the constituent proteins of a sample of sulfur-deficient human hair (trichothiodystrophy, TTD) which has a cystine content less than 50% of normal. The constituent low-sulfur proteins, although increased in amount, appear normal (apart from the absence of one minor component) as they contain the same array of subunit polypeptides covering the same range of molecular weights and isoelectric points as normal hair. In contrast, the high-sulfur proteins not only were decreased from the normal 40–45% to less than 10% but the proteins were on average smaller, had a lower than normal cystine content, and had a greatly altered amino acid composition. Fractionation followed by two-dimensional electrophoresis of the fractions revealed that the TTD high-sulfur proteins had lost the large heterogeneous group of ultrahigh-sulfur proteins and at least 8 major high-sulfur protein components but had acquired at least 22 components of lower than normal cystine content, which are either not present in normal human hair or are present at levels too low for detection. It is suggested, on the basis of nutritional studies on sheep and humans, that the loss of the ultrahigh-sulfur proteins is due to the presence of a sulfur-deficiency state, presumably of metabolic origin. The changes in the other high-sulfur proteins may be due to the mutation having affected the operation of a regulatory gene for high-sulfur proteins, as such changes do not occur in wool or hair as a result of dietary manipulation