title: A role for the 1A and L1 rod domain segments in head domain organization and function of intermediate filaments: structural analysis of trichocyte keratin.
abstract: A dynamic model is proposed to explain how the 1A and linker L1 segments of the rod domain in intermediate filament (IF) proteins affect the head domain organization and vice versa. We have shown in oxidized trichocyte IF that the head domain sequences fold back over and interact with the rod domain. This phenomenon may occur widely in reduced IF as well. Its function may be to stabilize the 1A segments into a parallel two-stranded coiled coil or something closely similar. Under differing reversible conditions, such as altered states of IF assembly, or posttranslational modifications, such as phosphorylation etc., the head domains may no longer associate with the 1A segment. This could destabilize segment 1A and cause the two alpha-helical strands to separate. Linker L1 would thus act as a hinge and allow the heads to function over a wide lateral range. This model has been explored using the amino acid sequences of the head (N-terminal) domains of Type I and Type II trichocyte keratin intermediate filament chains. This has allowed several quasi-repeats to be identified. The secondary structure corresponding to these repeats has been predicted and a model has been produced for key elements of the Type II head domain. Extant disulfide cross-link data have been used as structural constraints. A model for the head domain structure predicts that a twisted beta-sheet region may wrap around the 1A segment and this may reversibly stabilize a coiled-coil conformation for 1A. The evidence in favor of the swinging head model for IF is discussed.
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand. D.Parry@Massey.ac.nz
authors.forename: David A D
authors.initials: DA
authors.lastname: Parry
authors.forename: Lyuben N
authors.initials: LN
authors.lastname: Marekov
authors.forename: Peter M
authors.initials: PM
authors.lastname: Steinert
authors.forename: Thomasin A
authors.initials: TA
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides; D006801:Humans; D007633:Keratins / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012756:Sheep
chemical_list: D004220:Disulfides; D007633:Keratins