Pathways & interactions
Intermediate filament, rod domain (IPR039008)
Short name: IF_rod_dom
Overlapping homologous superfamilies
Intermediate filaments (IF) [PMID: 2183847, PMID: 28101862] are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide. IF proteins are members of a very large multigene family of proteins which has been subdivided in six types:
- Type I: Acidic cytokeratins.
- Type II: Basic cytokeratins.
- Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin.
- Type IV: Neurofilaments L, H and M, alpha-internexin and nestin.
- Type V: Nuclear lamins A, B1, B2 and C.
- Type VI: 'Orphan' IF proteins, which are more distant in terms of their amino acid sequences.
All IF proteins are structurally similar in that they consist of: a central rod domain comprising some 300 to 350 residues which is arranged in coiled- coiled alpha-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins.
While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain. The IF rod domain is approximately 310 residues long in all cytoplasmic IF proteins and close to 350 residues in the nuclear ones. The IF rod domain exhibits an interrupted alpha-helical conformation and reveals a pronounced seven-residue periodicity in the distribution of apolar residues. The heptad periodicity within the rod domain is interrupted in several places, which generates four consecutive alpha-helical segments: 1A and 1B, which together form the so-called coil 1, and 2A and 2B, which form coil 2. The four alpha-helical segments are interconnected by relatively short, variable linkers L1, L12 and L2 [PMID: 12596228, PMID: 22869704].
IF proteins have a very strong tendency to dimerize via the formation of an alpha-helical coiled coil (CC) by their rod domains [PMID: 22869704].