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Keratin intermediate filaments are an essential and major component of the
cytoskeleton in epithelial cells. They form a stable yet dynamic
filamentous network extending from the nucleus to the cell periphery,
which provides resistance to mechanical stresses. Mutations in keratin
genes are related to a variety of epithelial tissue diseases. Despite
their importance, the molecular structure of keratin filaments remains
largely unknown. In this study, we analyzed the structure of keratin
5/keratin 14 filaments within ghost keratinocytes by cryo-electron
microscopy and cryo-electron tomography. By averaging a large number of
keratin segments, we have gained insights into the helical architecture of
the filaments. Two-dimensional classification revealed profound variations
in the diameter of keratin filaments and their subunit organization.
Reconstitution of filaments of substantial length uncovered a high degree
of internal heterogeneity along single filaments, which can contain
regions of helical symmetry, regions with less symmetry and regions with
significant diameter fluctuations. Cross section views of filaments
revealed that keratins form hollow cylinders consisting of multiple
protofilaments, with an electron dense core located in the center of the
filament. These findings shed light on the complex and remarkable
heterogenic architecture of keratin filaments, suggesting that they are
highly flexible, dynamic cytoskeletal structures.
429 views reported since publication in 2021.