PROSITE documentation PDOC00198Intermediate filament (IF) rod domain signature and profile
Intermediate filaments (IF) [1,2,3,4] 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, α-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 (see <PDB:3G1E>) 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 [5,6].
IF proteins have a very strong tendency to dimerize via the formation of an α-helical coiled coil (CC) by their rod domains [6].
We use, as a sequence pattern for this class of proteins, a conserved region situated at the very end of the 2B segment, which is critically involved in specific dimer-dimer interactions within the mature filament [5]. We also developed a profile that covers the whole IF rod domain.
Note:In the third position of the pattern, Ala is found in type IV and V IF proteins, Thr is found in IF proteins of type I, II, III, and VI, Cys in IF from snails, and Ile in IF from worms. In the first position of the pattern Val is found in type VI, Ile is found in all other types.
Last update:September 2017 / Text revised; profile added.
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PROSITE methods (with tools and information) covered by this documentation:
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| PubMed ID | 2183847 |
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| Title | Crystallographic Studies of Intermediate Filament Proteins. | |
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| PubMed ID | 28101862 | |
| DOI | 10.1007/978-3-319-49674-0_6 |
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| Title | Molecular architecture of intermediate filaments. | |
| Source | Bioessays 25:243-251(2003). | |
| PubMed ID | 12596228 | |
| DOI | 10.1002/bies.10246 |
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| Title | Atomic structure of the vimentin central alpha-helical domain and its implications for intermediate filament assembly. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 109:13620-13625(2012). | |
| PubMed ID | 22869704 | |
| DOI | 10.1073/pnas.1206836109 |
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