Sequence analyses of Type I and Type II chains in human hair and epithelial keratin intermediate filaments: promiscuous obligate heterodimers, Type II template for molecule formation and a rationale for heterodimer formation.
Sequence comparisons have been undertaken for all hair and epithelial keratin IF chains from a single species--human. The results lead to several new proposals. First, it is clear that not only is the chain structure of the molecule an obligate heterodimer but promiscuous association of Type I and Type II chains must occur in vivo. Second, the higher predicted content of alpha-helix in Type II chains in solution relative to that expected for Type I chains suggests that it is the Type II chains that precede their Type I counterparts and that they may serve as templates for molecule formation. Third, heterodimer formation leads naturally to greater structural and functional specificity, and this may be required not only because keratin IF have more interacting partners in its cell type than other types of IF have in theirs but also because hair and skin IF have two distinct structures that relate to the "reducing" or "oxidizing" environment in which they can find themselves. The transition between the two forms may require specific head/tail interactions and this, it is proposed, would be more easily accomplished by a heterodimer structure with its greater in-built specificity.
Smith
Thomasin A
TA
Institute of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand.
Parry
David A D
DA
D000595:Amino Acid Sequence; D019281:Dimerization; D004848:Epithelium / Q000378:metabolism; D006197:Hair / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000737:chemistry; D053530:Keratins, Type I / Q000737:chemistry*; D053531:Keratins, Type II / Q000737:chemistry*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D020539:Sequence Analysis, Protein; D013816:Thermodynamics
D053530:Keratins, Type I; D053531:Keratins, Type II; D007633:Keratins