Intermediate filaments (IF) [ PUBMED:2183847 PUBMED: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 … expand

Intermediate filaments (IF) [ PUBMED:2183847 PUBMED: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 α-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 α-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 α-helical segments: 1A and 1B, which together form the so-called coil 1, and 2A and 2B, which form coil 2. The four α-helical segments are interconnected by relatively short, variable linkers L1, L12 and L2 [ PUBMED:12596228 PUBMED:22869704 ].

IF proteins have a very strong tendency to dimerize via the formation of an α-helical coiled coil (CC) by their rod domains [ PUBMED:22869704 ].