title: Dissecting the 3-D structure of vimentin intermediate filaments by cryo-electron tomography.
abstract: Vimentin polymerizes via complex lateral interactions of coiled-coil dimers into long, flexible filaments referred to as intermediate filaments (IFs). Intermediate in diameter between microtubules and microfilaments, IFs constitute the third cytoskeletal filament system of metazoan cells. Here we investigated the molecular basis of the 3-D architecture of vimentin IFs by cryo-electron microscopy (cryo-EM) as well as cryo-electron tomography (Cryo-ET) 3-D reconstruction. We demonstrate that vimentin filaments in cross-section exhibit predominantly a four-stranded protofibrilar organization with a right-handed supertwist with a helical pitch of about 96 nm. Compact filaments imaged by cryo-EM appear surprisingly straight and hence appear very stiff. In addition, IFs exhibited an increased flexibility at sites of partial unraveling. This is in strong contrast to chemically fixed, negatively stained preparations of vimentin filaments that generally exhibit smooth bending without untwisting. At some point along the filament unraveling may be triggered and propagates in a cooperative manner so that long stretches of filaments appear to have unraveled rapidly in a coordinated fashion.
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Lab, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Goldie
authors.forename: Tatjana
authors.initials: T
authors.lastname: Wedig
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mitra
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoenger
mesh_terms: D020285:Cryoelectron Microscopy; D006801:Humans; D011487:Protein Conformation; D014746:Vimentin / Q000648:ultrastructure*
chemical_list: D014746:Vimentin