Keratins: Difference between revisions

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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>.
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 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 .
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> .


==Primary structures of keratins==
==Primary structures of keratins==


In humans there are 54 functional genes that code for keratins <ref>PMID:16831889</ref> <ref name="PMID15085952">PMID:15085952</ref>. The first sequences of human keratin cDNAs revealed that there are two distinct but homologous keratin families <ref name="PMID6186381">PMID:6186381</ref> <ref name="PMID6191871">PMID:6191871</ref>. These two distinct types were named as Type I keratin and Type II keratin <ref name="PMID6191871" />.  
In humans there are 54 functional genes that code for keratins <ref>PMID:16831889</ref> <ref name="PMID15085952">PMID:15085952</ref>. The first sequences of human keratin cDNAs revealed that there are two distinct but homologous keratin families <ref name="PMID6186381">PMID:6186381</ref> <ref name="PMID6191871" />. These two distinct types were named as Type I keratin and Type II keratin <ref name="PMID6191871" />.  


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.
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 show a central ~300 residue 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 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>.
 
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" />.


==Secondary structures of keratins==
==Secondary structures of keratins==

Revision as of 13:36, 27 August 2013

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 [1]. The keratins represent the largest branch within the super-family of intermediate-filament proteins [2] [3].

Intermediate filamentsIntermediate filaments

In most eukaryotic cells there are three major cytoskeletal systems: [4]

  • Microfilaments composed of actin subunits
  • Intermediate filaments
  • Microtubules composed of tubulin subunits

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 [5].

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 [6]. 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 [7] .

Primary structures of keratinsPrimary structures of keratins

In humans there are 54 functional genes that code for keratins [8] [9]. The first sequences of human keratin cDNAs revealed that there are two distinct but homologous keratin families [10] [6]. These two distinct types were named as Type I keratin and Type II keratin [6].

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 [9] [11]. 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 [10]. 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 [12].

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 [13] [14]. 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 [6].

Secondary structures of keratinsSecondary structures of keratins

Tertiary and quaternary structures of keratinsTertiary and quaternary structures of keratins

ReferencesReferences

  1. ↑ Moll R, Divo M, Langbein L. The human keratins: biology and pathology. Histochem Cell Biol. 2008 Jun;129(6):705-33. doi: 10.1007/s00418-008-0435-6. Epub, 2008 May 7. PMID:18461349 doi:10.1007/s00418-008-0435-6
  2. ↑ Godsel LM, Hobbs RP, Green KJ. Intermediate filament assembly: dynamics to disease. Trends Cell Biol. 2008 Jan;18(1):28-37. PMID:18083519 doi:10.1016/j.tcb.2007.11.004
  3. ↑ Eriksson JE, Dechat T, Grin B, Helfand B, Mendez M, Pallari HM, Goldman RD. Introducing intermediate filaments: from discovery to disease. J Clin Invest. 2009 Jul;119(7):1763-71. doi: 10.1172/JCI38339. Epub 2009 Jul 1. PMID:19587451 doi:10.1172/JCI38339
  4. ↑ Suozzi KC, Wu X, Fuchs E. Spectraplakins: master orchestrators of cytoskeletal dynamics. J Cell Biol. 2012 May 14;197(4):465-75. doi: 10.1083/jcb.201112034. PMID:22584905 doi:10.1083/jcb.201112034
  5. ↑ Wade RH. On and around microtubules: an overview. Mol Biotechnol. 2009 Oct;43(2):177-91. doi: 10.1007/s12033-009-9193-5. Epub 2009 , Jun 30. PMID:19565362 doi:10.1007/s12033-009-9193-5
  6. ↑ 6.0 6.1 6.2 6.3 Hanukoglu I, Fuchs E. The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins. Cell. 1983 Jul;33(3):915-24. PMID:6191871
  7. ↑ Godsel LM, Hobbs RP, Green KJ. Intermediate filament assembly: dynamics to disease. Trends Cell Biol. 2008 Jan;18(1):28-37. PMID:18083519 doi:10.1016/j.tcb.2007.11.004
  8. ↑ Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW. New consensus nomenclature for mammalian keratins. J Cell Biol. 2006 Jul 17;174(2):169-74. Epub 2006 Jul 10. PMID:16831889 doi:10.1083/jcb.200603161
  9. ↑ 9.0 9.1 Hesse M, Zimek A, Weber K, Magin TM. Comprehensive analysis of keratin gene clusters in humans and rodents. Eur J Cell Biol. 2004 Feb;83(1):19-26. PMID:15085952
  10. ↑ 10.0 10.1 Hanukoglu I, Fuchs E. The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins. Cell. 1982 Nov;31(1):243-52. PMID:6186381
  11. ↑ Schweizer J, Langbein L, Rogers MA, Winter H. Hair follicle-specific keratins and their diseases. Exp Cell Res. 2007 Jun 10;313(10):2010-20. Epub 2007 Mar 14. PMID:17428470 doi:10.1016/j.yexcr.2007.02.032
  12. ↑ Parry DA, Strelkov SV, Burkhard P, Aebi U, Herrmann H. Towards a molecular description of intermediate filament structure and assembly. Exp Cell Res. 2007 Jun 10;313(10):2204-16. Epub 2007 Apr 12. PMID:17521629 doi:10.1016/j.yexcr.2007.04.009
  13. ↑ Bragulla HH, Homberger DG. Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia. J Anat. 2009 Apr;214(4):516-59. PMID:19422428 doi:JOA1066
  14. ↑ Moll R, Divo M, Langbein L. The human keratins: biology and pathology. Histochem Cell Biol. 2008 Jun;129(6):705-33. doi: 10.1007/s00418-008-0435-6. Epub, 2008 May 7. PMID:18461349 doi:10.1007/s00418-008-0435-6

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Israel Hanukoglu, Liora Ezra, Michal Harel, Angel Herraez
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