26.16:
Formation of Intermediate Filaments
The formation of intermediate filaments within a cell is a multi-step process. Two monomeric subunits, interact side-by-side, or laterally to form a coiled-coil dimer.
As two oppositely oriented polar dimers associate, they form a nonpolar tetramer, the basic unit of any intermediate filament.
The tetramers then bind end-to-end to form a protofilament, which associates laterally with other protofilaments to form a protofibril, two to three nanometers wide.
When four such protofibrils come together, they coil laterally to form a unit-length filament. Each unit-length filament is about sixty nanometers long and ten nanometers wide.
These unit-length filaments further polymerize in a head-to-tail arrangement to form an intermediate filament.
26.16:
Formation of Intermediate Filaments
Intermediate filaments are cytoskeletal proteins with higher tensile strength and flexibility than microfilaments and microtubules. Unlike the other two cytoskeletal proteins, intermediate filament formation lacks the enzymatic activity to hydrolyze nucleotides like ATP and GTP to generate energy for polymerization. Therefore, the formation of intermediate filaments is multistep self-assembly. The involvement of any accessory proteins in intermediate filament formation has not yet been reported.
The multi-step process uses two types of associations: lateral association, i.e., side-to-side binding, and longitudinal association, i.e., head-to-tail binding. The monomeric core is similar across different intermediate filaments with a tripartite structure, with an α-helical rod domain flanked by two non-α-helical domains. The formation starts with the lateral association of two monomers forming a dimer. Depending on the type of monomer, the dimer can be homodimeric, made up of identical monomers, or heterodimeric, made up of two different types of monomers. These dimers then associate in an antiparallel manner to form a tetramer. Eight tetramers associate laterally to form a bundle, called the unit length filament or ULF. The ULF is 60 nm in length and 10 nm in diameter. These unit-length filaments arrange in a head-to-tail manner to form the intermediate filaments.
Suggested Reading
- Herrmann, H. and Aebi, U., 2016. Intermediate filaments: structure and assembly. Cold Spring Harbor Perspectives in Biology, 8(11), p.a018242.
- Vermeire, P.J., Stalmans, G., Lilina, A.V., Fiala, J., Novak, P., Herrmann, H. and Strelkov, S.V., 2021. Molecular Interactions Driving Intermediate Filament Assembly. Cells, 10(9), p.2457.