Keratins: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Israel Hanukoglu, Liora Ezra, Michal Harel, Angel Herraez

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-Keratin is the name given to a large family of homologous proteins that have a filamentous (fibrous) structure. These proteins are expressed in epithelial cells and in epidermal cells where they they are assembled forming cytoskeletal structures within the cell and epidermal derivatives such as hair, nail and horn <ref>PMID:18461349</ref>. The keratins represent the largest branch within the super-family of intermediate-filament proteins  <ref>PMID:18083519</ref> <ref>PMID:19587451</ref>.
+Keratin is the name given to a large family of homologous proteins that have a filamentous (fibrous) structure. These proteins are expressed in epithelial cells and in epidermal cells where they they are assembled forming cytoskeletal structures within the cell and epidermal derivatives such as hair, nail and horn <ref>PMID:18461349</ref>.
+The keratins represent the largest branch within the super-family of intermediate-filament (IF) proteins  <ref name="PMID18083519">PMID:18083519</ref> <ref>PMID:19587451</ref>. Keratins are grouped into two families termed as type I and type II keratins based on their sequence homology <ref name="PMID6191871">PMID:6191871</ref>. Similarly, other IF proteins are also grouped into families termed consecutively as types III, IV, V and VI IF proteins, based on their sequence homology <ref>PMID:8982454</ref>. These families include desmin, vimentin, neurofilament protein and GFAP that are expressed in specific tissues and cell types <ref name="PMID18083519" />. The IF family of lamins are located on the nuclear lamina and  are ubiquitously expressed <ref name="PMID18083519" />.
 ==Intermediate filaments==
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 The name "intermediate filament" reflects the comparative morphology of these filaments as their diameter is about 8-12 nm;  a value that is "intermediate" between microfilaments with a diameter of 6-7 nm and microtubules with a diameter of 25 nm <ref>PMID:19565362</ref>.
-Both microfilaments and microtubules are assembled from globular subunits, actin and tubulin respectively. In contrast, intermediate filaments (IFs) are composed of proteins that have a long fibrous structure that results from long stretches of alpha helical domains and a fiber like coiled-coil structure of two subunits that are wrapped together. Each keratin filament is composed of two homologous keratins, named as type I and type II keratins <ref name="PMID6191871 ">PMID:6191871</ref>. There are additional types of proteins that form IFs. These include desmin, vimentin, neurofilament protein and GFAP that are expressed in specific tissues and cell types. The IF family of lamins are located on the nuclear lamina and  are ubiquitously expressed <ref>PMID:18083519</ref> .
+Both microfilaments and microtubules are assembled from globular subunits of actin and tubulin respectively. In contrast, intermediate filaments (IFs) are composed of proteins that have a long fibrous structure that results from long stretches of alpha helical domains.
+The basic building block of each intermediate filament is a dimer of a coiled-coil pair of IF proteins. Each keratin filament is assembled as a hetero-dimer of a type I keratin coiled together with a type II keratin. <ref name="PMID6191871 ">PMID:6191871</ref>. Other types of IFs are mostly composed of homo-dimers <ref name="PMID18083519" />.
 ==Primary structures of keratins==
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 Human genome sequencing revealed that type I and type II keratin genes are located in two clusters each of which includes 27 genes on chromosome 17q21 and on chromosome 12q13 respectively <ref name="PMID15085952" /> <ref>PMID:17428470</ref>. The juxtaposed location of the genes indicate that these gene clusters evolved by a series of gene duplication events.
-Determination of the sequences of type I and type keratins revealed that the two types of keratins have a central ~300 residue long segment that shows ~30% homology between the two types of proteins, but the amino and carboxy terminal regions of these proteins show great diversity <ref name="PMID6186381" />. Consistent with the initial observations, sequencing of keratins and other intermediate filament proteins showed all IF proteins have a conserved central domain and widely divergent amino and carboxy terminal regions <ref>PMID: 17521629</ref>.
+Determination of the sequences of type I and type keratins revealed that the two types of keratins have a central ~300 residue long segment that show ~30% homology, but the amino and carboxy terminal regions of these proteins show great diversity <ref name="PMID6186381" />. Consistent with the initial observations, sequencing of keratins and other intermediate filament proteins showed that all IF proteins have a conserved central domain and widely divergent amino and carboxy terminal regions <ref>PMID: 17521629</ref>.
-Sequencing and two dimensional gel electrophoresis of the complete family of keratins showed that the type I and type II keratins distinct differences in their size and isolelectric points <ref>PMID:19422428</ref> <ref>PMID:18461349</ref>. Type I keratins are generally smaller (average length 460 aa's), and acidic (isoelectric point 4.4-5.4), while type II keratins are longer (average length 545 aa's) and basic (isoelectric point 5-8.3). As noted, the size differences among keratins result from differences in the amino and carboxy terminals of the proteins <ref name="PMID6191871" />.
+Sequencing and two dimensional gel electrophoresis of the complete family of keratins revealed that the type I and type II keratins differ in their size and isolelectric points <ref>PMID:19422428</ref> <ref>PMID:18461349</ref>. Type I keratins are generally smaller (average length 460 aa's), and acidic (isoelectric point 4.4-5.4), while type II keratins are longer (average length 545 aa's) and basic (isoelectric point 5-8.3). As noted, the size differences among keratins result from differences in the amino and carboxy terminals of the proteins <ref name="PMID6191871" />.
 ==Secondary structures of keratins==
+The first model of alpha-helix was proposed by Pauling based on the crystallography of wool fibers <ref>PMID:12966187</ref> that were shown to have long helical segments <ref>PMID:6072928</ref>.
+Analysis of the first cytoskeletal keratin sequence revealed that this protein contains a central domain of ~300 residues that was predicted to be mostly in alpha helix conformation <ref name="PMID6186381" />. By comparative analysis of the predicted structures of a type I keratin, a type II keratin, desmin and vimentin, Hanukoglu and Fuchs suggested that all IF proteins have a central ~300 residue domain that contains four segments in alpha helical conformation that are separated by three short linker segments predicted to be in beta-turn conformation <ref name="PMID6191871" />. This model has been confirmed by analysis of the crystal structure of segments of keratin coiled-coil <ref>PMID:10998598</ref>.