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

SV Strelkov, H Herrmann, N Geisler, T Wedig… - The EMBO …, 2002 - embopress.org
SV Strelkov, H Herrmann, N Geisler, T Wedig, R Zimbelmann, U Aebi, P Burkhard
The EMBO journal, 2002embopress.org
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 α‐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 …
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 α‐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 α‐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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