A Role for the 1A and L1 Rod Domain Segments in Head Domain Organization and Function of Intermediate Filaments: Structural Analysis of Trichocyte Keratin

Sequence Comparisons of Intermediate Filament Chains: Evidence of a Unique Functional/Structural Role for Coiled-Coil Segment 1A and Linker L1

“…(10) The splayed structure of the end of segment 2B determined by X-ray crystallography and the proposed separation of the ␣-helical strands in segment 1A allow the possibility of the head-to-tail overlap between parallel molecules being structurally equivalent to a bundle of four parallel ␣-helices. The data presented here support the hypothesis that segment 1A is capable of adopting either a two-stranded coiled-coil rope structure or that of two distinct ␣-helical strands (Parry et al, 2002;. In the former case the head domains would likely fold back over segment 1A (and possibly linker L1 and segment 1B) and hence stabilize the coiled-coil rope structure.…”

“…This suggests that the head domains are required for coiled-coil formation of segment 1A. Experimental evidence for head interaction with segment 1A has also been presented for trichocyte keratin by Wang et al, (2000) and Parry et al (2002). It has also been noted that the sequence of segment 1A differs in important ways from those of other rod domain segments in intermediate filament molecules (Parry et al, 2002).…”

“…Experimental evidence for head interaction with segment 1A has also been presented for trichocyte keratin by Wang et al, (2000) and Parry et al (2002). It has also been noted that the sequence of segment 1A differs in important ways from those of other rod domain segments in intermediate filament molecules (Parry et al, 2002). For example, segment 1A contains no strongly developed period in the linear distribution of acidic and the basic residues, unlike that in segments 1B and 2B (Crewther et al, 1983).…”

“…Taken together, the above-described data have allowed the suggestion to be made that segment 1A alternates between a two-stranded coiled-coil rope and two separate ␣-helical strands, with linker L1 acting as a flexible hinge (Parry et al, 2002;. Such a scheme, if correct, would allow the head domains to move laterally over a much greater distance than would otherwise be possible.…”

The role of β-sheets in the structure and assembly of keratins

“…The head region (N-terminal domain) of the Type II trichocyte keratin chain contains a fourfold contiguous repeat of nine residues (G-G-F-G-Y-R-S-X-G). This too is thought to adopt a β-pleated sheet conformation but in this case, there is not a clear chemical sidedness to the two faces (Parry et al 2002). It would still be expected, nonetheless, that this sheet would interact with the same region emanating from a second molecule.…”