title: Diversity of intermediate filament structure. Evidence that the alignment of coiled-coil molecules in vimentin is different from that in keratin intermediate filaments.
abstract: Although vimentin intermediate filaments (IF) are morphologically similar to all other IF types, cells have evolved different ways of manipulating vimentin and keratin IF. The structural basis for such differences is unknown. We have explored this by use of cross-linking experiments on vimentin oligomers, polymers, and intact IF to determine the axial length of vimentin molecules and the degrees to which neighboring molecules are aligned in IF. Our data reveal that the homodimer vimentin molecule (43.9 nm) is clearly shorter than a keratin heterodimer molecule (46.2 nm). Vimentin assemblies contain three modes of antiparallel molecular alignments: A11 and A22 in two-molecule or larger oligomeric assemblies, in which the two molecules are staggered so as to bring their 1B and 2B rod domain segments, respectively, into register; and A12 in higher order molecular assemblies in which the two neighboring molecules are largely overlapped. Since the repeat axial length of the vimentin assemblies (42.6 nm) is less than the molecular length, this means there is an overlap (designated as alignment ACN) of about 1 nm (5-10 residues) between the end of the 2B and beginning of the 1A rod domain segments of similarly directed molecules in the IF. Interestingly, these four modes of nearest neighbor molecular alignments also occur in keratin IF. However, the degree of stagger of alignments in the A11 and A22 modes is different (staggers of -19.5 for vimentin versus -16.6 nm for keratin, and 23.3 and 28.6 nm, respectively). Two-dimensional surface lattice maps of the two IF types are very similar, except for differences in molecule alignments and different axial repeats of 21.4 nm in vimentin and 22.6 nm in keratin IF. Although vimentin-keratin hybrid molecules can be induced to form in vitro, they do not assemble into higher order structures. The data suggest that vimentin and keratin are incapable of assembly into IF in vitro or in vivo simply because their molecules are of different axial lengths and because the exact axial alignments of neighboring molecules are different.
authors.affiliation: Skin Biology Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: P M
authors.initials: PM
authors.lastname: Steinert
authors.forename: L N
authors.initials: LN
authors.lastname: Marekov
authors.forename: D A
authors.initials: DA
authors.lastname: Parry
mesh_terms: D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents; D006801:Humans; D007382:Intermediate Filaments / Q000737:chemistry* / Q000648:ultrastructure; D007633:Keratins / Q000737:chemistry* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011108:Polymers; D011487:Protein Conformation; D014746:Vimentin / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D003432:Cross-Linking Reagents; D011108:Polymers; D014746:Vimentin; D007633:Keratins