Human fibrinogen contains 29 disulfide bonds, only three of which are involved in holding the two dimeric halves of the molecule together. Of the remainder, twelve others are arranged in four sets of three bonds each. Thus, each half of the molecule has two of these unusual arrangements separated by a three-stranded rope consisting of approximately 110 residues in each chain. Alignment of the three non-identical chains at the appropriate cysteine residues participating in these assemblies has revealed not only significant homology but also a rhythmic occurrence of polar and nonpolar amino acids consistent with the existence of coiled α-helices. Indeed, other workers had predicated the existence of such coiled-coils on the basis of fiber diffraction studies a generation ago, hypothesizing that they were likely inter-domainal connections holding the distal portions of a Hall and Slayter-type molecule to the central region. Our data indicate that these predictions were essentially correct. To reinforce the point we have constructed a detailed molecular model of the connecting regions, even to the point where the hypothetical atomic coordinates have been recorded. The model is consistent with virtually all physical data and illuminates details of how molecular packing may occur during formation. It also delineates the geography of bond splitting during fibrinolysis, especially with regard to the boundaries of fragments D and E.
The cDNA-deduced amino acid sequence for trichohyalin, a differentiation marker in the hair follicle, contains a 23 amino acid repeat.
