| Intermediate filament tail domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| structure of lamin a/c globular domain | |||||||||
| Identifiers | |||||||||
| Symbol | IF_tail | ||||||||
| Pfam | PF00932 | ||||||||
| InterPro | IPR001322 | ||||||||
| PROSITE | PDOC00198 | ||||||||
| SCOP | 1ivt | ||||||||
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| Intermediate filament protein | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| human vimentin coil 2b fragment (cys2) | |||||||||
| Identifiers | |||||||||
| Symbol | Filament | ||||||||
| Pfam | PF00038 | ||||||||
| InterPro | IPR016044 | ||||||||
| PROSITE | PDOC00198 | ||||||||
| SCOP | 1gk7 | ||||||||
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| Intermediate filament head (DNA binding) region | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Filament_head | ||||||||
| Pfam | PF04732 | ||||||||
| InterPro | IPR006821 | ||||||||
| SCOP | 1gk7 | ||||||||
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Intermediate filaments (IFs) are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin (microfilaments), and that of 25 nm microtubules, although they were initially designated 'intermediate' because their average diameter is between those of narrower microfilaments (actin) and wider myosin filaments.[1] Most types of intermediate filaments are cytoplasmic, but one type, the lamins, are nuclear.
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The domain structure of IF molecules is conserved. Each protein has a non-alpha-helical (globular) domain at the N and C-termini, which surrounds the alpha-helical rod domain. The basic building-block for IFs is a parallel and in-register dimer. The dimer is formed through the interaction of the rod domain to form a coiled coil.[2] Cytoplasmic IF assemble into non-polar unit-length filaments (ULF), which then assemble into longer structures. Part of the assembly process includes a compaction step, in which ULF tighten and assume a smaller diameter. The reasons for this compaction are not well understood, and IF are routinely observed to have diameters ranging between 6 and 12 nm.
The N-terminal "head domain" binds DNA.[3] Vimentin heads are able to alter nuclear architecture and chromatin distribution, and the liberation of heads by HIV-1 protease may play an important role in HIV-1 associated cytopathogenesis and carcinogenesis.[4] Phosphorylation of the head region can affect filament stability.[5] The head has been shown to interact with the rod domain of the same protein.[6]
C-terminal "tail domain" shows extreme length variation between different IF proteins.[7]
The anti-parallel orientation of tetramers means that, unlike microtubules and microfilaments, which have a plus end and a minus end, IFs lack polarity.
Also, as opposed to actin or tubulin, intermediate filaments do not contain a binding site for a nucleoside triphosphate.
Cytoplasmic IF do not undergo treadmilling like microtubules and actin fibers, but they are dynamic. For a review see: [1].
IFs are rather deformable proteins that can be stretched several times their initial length.[8] The key to facilitate this large deformation is due to their hierarchical structure, which facilitates a cascaded activation of deformation mechanisms at different levels of strain.[2]
There are about 70 different genes coding for various intermediate filament proteins. However, different kinds of IFs share basic characteristics: In general, they are all polymers that measure between 9-11 nm in diameter when fully assembled.
IF are subcategorized into six types based on similarities in amino acid sequence and protein structure.
These proteins are the most diverse among IFs and constitute type I (acidic) and type II (basic) IF proteins. The many isoforms are divided in two groups:
Regardless of the group, keratins are either acidic or basic. Acidic and basic keratins bind each other to form acidic-basic heterodimers and these heterodimers then associate to make a keratin filament.
There are four proteins classed as type III IF proteins, which may form homo- or heteropolymeric proteins.
Lamins are fibrous proteins having structural function in the cell nucleus.
In metazoan cells, there are A and B type lamins, which differ in their length and pI. Human cells have three differentially regulated genes. B-type lamins are present in every cell. B type lamins, B1 and B2, are expressed from the LMNB1 and LMNB2 genes on 5q23 and 19q13, respectively. A-type lamins are only expressed following gastrulation. Lamin A and C are the most common A-type lamins and are splice variants of the LMNA gene found at 1q21.
These proteins localize to two regions of the nuclear compartment, the nuclear lamina—a proteinaceous structure layer subjacent to the inner surface of the nuclear envelope and throughout the nucleoplasm in the nucleoplasmic "veil".
Comparison of the lamins to vertebrate cytoskeletal IFs shows that lamins have an extra 42 residues (six heptads) within coil 1b. The c-terminal tail domain contains a nuclear localization signal (NLS), an Ig-fold-like domain, and in most cases a carboxy-terminal CaaX box that is isoprenylated and carboxymethylated (lamin C does not have a CAAX box). Lamin A is further processed to remove the last 15 amino acids and its farnesylated cysteine.
During mitosis, lamins are phosphorylated by MPF, which drives the disassembly of the lamina and the nuclear envelope.
Beaded Filaments-- Filensin, Phakinin
At the plasma membrane, some keratins interact with desmosomes (cell-cell adhesion) and hemidesmosomes (cell-matrix adhesion) via adapter proteins.
Filaggrin binds to keratin fibers in epidermal cells. Plectin links vimentin to other vimentin fibers, as well as to microfilaments, microtubules, and myosin II.
Keratin filaments in epithelial cells link to desmosomes (desmosomes connect the cytoskeleton together) through plakoglobin, desmoplakin, desmogleins, and desmocollins; desmin filaments are connected in a similar way in heart muscle cells.
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This article incorporates text from the public domain Pfam and InterPro IPR001322
This article incorporates text from the public domain Pfam and InterPro IPR006821