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  • The EMBO Journal (2002) 21, 1255 - 1266
  • doi:10.1093/emboj/21.6.1255

Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly

Sergei V. Strelkov1, Harald Herrmann2, Norbert Geisler3, Tatjana Wedig2, Ralf Zimbelmann2, Ueli Aebi1 and Peter Burkhard1

  1. Maurice E.Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
  2. Division of Cell Biology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg Germany
  3. Division of Biochemistry and Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fas zligberg 11, D-37070, Göttingen, Germany

Correspondence to:

Sergei V. Strelkov, E-mail: sergei-v.strelkov@unibas.ch

Received 8 October 2001; Accepted 22 January 2002; Revised 14 January 2002

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 Å 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.

  • Keywords:

    • atomic structure,
    • coiled coil,
    • intermediate filaments,
    • vimentin,
    • X-ray crystallography