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| Subject Categories: Structural Biology | Cell & Tissue Architecture |
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| The EMBO Journal
(2002) 21, 1255–1266, doi: 10.1093/emboj/21.6.1255 |
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| Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly |
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| Sergei V. Strelkov1, Harald Herrmann2, Norbert Geisler3, Tatjana Wedig2, Ralf Zimbelmann2, Ueli Aebi1 and Peter Burkhard1 |
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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 Fa  berg 11, D-37070, Göttingen, GermanyTo whom correspondence should be addressed Sergei V. Strelkov, sergei-v.strelkov@unibas.ch Received 8 October 2001; Revised 14 January 2002; Accepted 22 January 2002. |
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| Abstract |
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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  -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 -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. |
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| Keywords: atomic structure, coiled coil, intermediate filaments, vimentin, X-ray crystallography |
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