Characterization of the Type-1 Repeat from Thyroglobulin, a Cysteine-Rich Module Found in Proteins from Different Families


  • Supplementary material.Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families. Table S1. Alignment of amino acid sequences of thyroglobulin type-I motifs. Table S2. PIRALIN alignment and derived consensus sequence of EGF-like modules. Fig. S1. rss statistical analysis of the similarity between EGF-like modules and thyroglobulin type-I A motifs. This information is available, on request, from the Editorial Office. Five pages are available.

F. Molina, CNRS UMR 9921, Faculté de Pharmacie, 15 avenue Charles Flahault, F-34060 Montpellier-Cedex 1, France


The amino acid sequence of human thyroglobulin is known to enclose cysteine-rich repetitive regions. In this study, we report the existence of an eleventh type-1 repeat within the human thyroglobulin sequence, and we characterize the thyroglobulin type-1 repeat as a protein module. The 11 thyroglobulin type-1 repeats possessed the same number of cysteine residues (six in type A, four in the two type B repeats), a fairly constant number of residues between cysteines and a conserved sequence pattern. By scanning protein sequence databases, 29 proteins belonging to six different families were found to enclose at least one, and up to three, thyroglobulin type-1 repeats in their sequence. Although the repeat was present in numerous proteins possessing binding properties, an examination of the information available in the literature showed that a direct role of the repeat in protein-protein interaction has rarely been assessed. A distance analysis of the sequences indicated that all repeats segregate into four clusters of phylogenically close sequences. A consensus sequence of type-1 repeats was derived from sequence similarity analysis; it comprised a central core of conserved residues including two highly conserved motifs, QC and CWCV. The type-1 repeat from thyroglobulin was found to differ from several previously described cysteine-rich modules, in particular from the epidermal-growth-factor-like module with which it has sometimes been confused. Therefore, our results provide a complete characterization of the repeats which will help in the detection of these repeats in newly characterized proteins, a necessary step for understanding the structural/biological role of this module.