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Strelkov, SV, Herrmann, H, Geisler, N, Wedig, T, Zimbelmann, R, Aebi, U and Burkhard, P (2002) Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly. EMBO J. 21:1255-66

Intermediate filaments (IFs) are key components of the cytoskeleton in higher eukaryotic cells. The elementary IF 'building block' is an elongated coiled-coil dimer consisting of four consecutive alpha-helical segments. The segments 1A and 2B include highly conserved sequences and are critically involved in IF assembly. Based on the crystal structures of three human vimentin fragments at 1.4-2.3 A resolution (PDB entries 1gk4, 1gk6 and 1gk7), we have established the molecular organization of these two segments. The fragment corresponding to segment 1A forms a single, amphipatic alpha-helix, which is compatible with a coiled-coil geometry. While this segment might yield a coiled coil within an isolated dimer, monomeric 1A helices are likely to play a role in specific dimer-dimer interactions during IF assembly. The 2B segment reveals a double-stranded coiled coil, which unwinds near residue Phe351 to accommodate a 'stutter'. A fragment containing the last seven heptads of 2B interferes heavily with IF assembly and also transforms mature vimentin filaments into a new kind of structure. These results provide the first insight into the architecture and functioning of IFs at the atomic level.

PubMed PMC125921 Online version:10.1093/emboj/21.6.1255

Amino Acid Sequence; Conserved Sequence; Crystallography, X-Ray; Dimerization; Humans; Intermediate Filaments/metabolism; Intermediate Filaments/physiology; Models, Molecular; Molecular Sequence Data; Protein Structure, Secondary; Sequence Homology, Amino Acid; Vimentin/chemistry; Vimentin/metabolism; Vimentin/physiology