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Titin, or Connectin, is the largest protein that has so far been discovered, undertaking the role of a structural and mechanical molecule, and it is commonly found in the [[Myofibril|myofibrils]] of skeletal [[Skeletal Muscle|muscle fibres]]. Within each [[Sarcomere|sarcomere]] they act as stable, long, elastic filaments that run from the Z disc to the M line region&nbsp;<ref>Nunes J.M., Hensen U, Ge L, Lipinsky M, Helenius J, Grubmüller H, Muller D.J. (2010) Angewandte Chemie International Edition, Volume 49 Issue 20, pp.3528-3531. [ONLINE] Available at http://onlinelibrary.wiley.com.libproxy.ncl.ac.uk/doi/10.1002/anie.200906388/full [Accessed 29 November 2012].</ref>. Its main function is to help stop muscles from over-stretching, or over-relaxing, by acting as a flexible and dynamic shock absorber . They are able to contract, tighten or even shrink in order to redirect the energy output whenever muscles stretch.  
Titin, or Connectin, is the largest protein that has so far been discovered, undertaking the role of a structural and mechanical molecule, and it is commonly found in the [[Myofibril|myofibrils]] of skeletal [[Skeletal muscle|muscle fibres]]. Within each [[Sarcomere|sarcomere]] it acts as a stable, long, elastic filament that run from the Z disc to the M line region <ref>Nunes J.M., Hensen U, Ge L, Lipinsky M, Helenius J, Grubmüller H, Muller D.J. (2010) Angewandte Chemie International Edition, Volume 49 Issue 20, pp.3528-3531 [Peer Reviewed Journal]. [ONLINE] Available at http://onlinelibrary.wiley.com.libproxy.ncl.ac.uk/doi/10.1002/anie.200906388/full [Accessed 29 November 2012].</ref>. Its main function is to help stop muscles from over-stretching, or over-relaxing, by acting as a flexible and dynamic shock absorber <ref>Benichou I, Givli S (2011) Applied Physics Letters 98, 091904: The Hidden Ingenuity in Titin Structure [Peer Reviewed Journal] The American Institue of Physics. [ONLINE] Available at http://apl.aip.org.libproxy.ncl.ac.uk/resource/1/applab/v98/i9/p091904_s1 [Accessed 29 November 2012].</ref>. They can contract, tighten or even shrink to redirect the energy output whenever muscles stretch.  


The titin protein is encoded by a single [[Gene|gene]], and in humans is known to have 363 [[Exon|exons]] that code for around 38,000 [[Amino acid|amino acids]] (3).  
The titin protein is encoded by a single [[Gene|gene]], and in humans is known to have 363 [[Exon|exons]] that code for around 38,000 [[Amino acids|amino acids]] <ref>Granzier H.L., Labeit S (2004) Circulation Research 94: page 284-295: The Giant Protein Titin, American Heart Association. [ONLINE] Available at http://circres.ahajournals.org/content/94/3/284.full [Accessed 29 November 2012].</ref>. Skeletal muscle titin is 3,700 kDa and measures 2 µm in length ''in vivo'' <ref>The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.Bang ML et al. http://www.ncbi.nlm.nih.gov/pubmed/11717165</ref>.  


In the myofibril, titin helps place and align the thick [[Myosin|myosin]] filaments between the Z discs within the middle of the sarcomere. It contains long chains of specific domains that resemble [[Immunoglobulin|immunoglobulins]] – it is these domains that give the protein its characteristic spring-like elasticity. They can fold and unfold to maintain the structural arrangement of the thick filaments over the M line when the protein is undergoing stress or compression (3), thus acting as an entropic spring (4).  
In the myofibril, Titin helps place and align the thick [[Myosin|myosin]] filaments between the Z discs within the middle of the sarcomere. It contains long chains of specific domains that resemble [[Immunoglobulin|immunoglobulins]] – it is these domains that give the protein its characteristic spring-like elasticity. They can fold and unfold to maintain the structural arrangement of the thick filaments over the M line when the protein is undergoing stress or compression <ref>Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular Biology of The Cell, page 1028, 5th edition, New York: Garland Science.</ref>, thus acting as an entropic spring <ref>Erickson, H.P. (1997) Science, Volume 276 No 5315, page 1090-1092 Stretching Single Protein Molecules: Titin is a Weird Spring [Peer Reviewed Journal]. [ONLINE] Available at http://www.sciencemag.org.libproxy.ncl.ac.uk/content/276/5315/1090 [Accessed 29 November 2012].</ref>.  


In recent experiments, it has been implied that titin shows traits of its function as a molecular ruler – where the sarcomere is longer, for example in the vertebrate ''[[C. elegans|C. Elegans]]'', the titin filaments are also longer, showing a relationship between the length of titin and the length of the sarcomeres (4).  
In recent experiments, it has been implied that titin shows traits of its function as a molecular ruler – where the [[Sarcomere|sarcomere]] is longer, for example in the vertebrate ''[[C. elegans|C. elegans]]'', the titin filaments are also longer, showing a relationship between the length of titin and the length of the sarcomeres <ref>Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular Biology of The Cell, page 1028, 5th edition, New York: Garland Science.</ref>.  


<br>  
Mutations in the titin gene have been associated with [[Tibial muscular dystrophy|tibial muscular dystrophy]] (TMD), an autosomal dominant distal myopathy <ref>TIBIAL MUSCULAR DYSTROPHY, TARDIVE. http://omim.org/entry/600334</ref>, with a late-onset of 35-45 years of age, or later <ref>Muscular dystrophy with separate clinical phenotypes in a large family. Udd B et al. http://www.ncbi.nlm.nih.gov/pubmed/1745277</ref>. The official symbol of Titin is TTN&nbsp;<ref name="Gene Profile on PubMed">https://www.ncbi.nlm.nih.gov/gene/7273</ref>.


=== '''References''' ===
=== References  ===


<references />
<references />

Latest revision as of 12:38, 16 November 2017

Titin, or Connectin, is the largest protein that has so far been discovered, undertaking the role of a structural and mechanical molecule, and it is commonly found in the myofibrils of skeletal muscle fibres. Within each sarcomere it acts as a stable, long, elastic filament that run from the Z disc to the M line region [1]. Its main function is to help stop muscles from over-stretching, or over-relaxing, by acting as a flexible and dynamic shock absorber [2]. They can contract, tighten or even shrink to redirect the energy output whenever muscles stretch.

The titin protein is encoded by a single gene, and in humans is known to have 363 exons that code for around 38,000 amino acids [3]. Skeletal muscle titin is 3,700 kDa and measures 2 µm in length in vivo [4].

In the myofibril, Titin helps place and align the thick myosin filaments between the Z discs within the middle of the sarcomere. It contains long chains of specific domains that resemble immunoglobulins – it is these domains that give the protein its characteristic spring-like elasticity. They can fold and unfold to maintain the structural arrangement of the thick filaments over the M line when the protein is undergoing stress or compression [5], thus acting as an entropic spring [6].

In recent experiments, it has been implied that titin shows traits of its function as a molecular ruler – where the sarcomere is longer, for example in the vertebrate C. elegans, the titin filaments are also longer, showing a relationship between the length of titin and the length of the sarcomeres [7].

Mutations in the titin gene have been associated with tibial muscular dystrophy (TMD), an autosomal dominant distal myopathy [8], with a late-onset of 35-45 years of age, or later [9]. The official symbol of Titin is TTN [10].

References

  1. ↑ Nunes J.M., Hensen U, Ge L, Lipinsky M, Helenius J, Grubmüller H, Muller D.J. (2010) Angewandte Chemie International Edition, Volume 49 Issue 20, pp.3528-3531 [Peer Reviewed Journal]. [ONLINE] Available at http://onlinelibrary.wiley.com.libproxy.ncl.ac.uk/doi/10.1002/anie.200906388/full [Accessed 29 November 2012].
  2. ↑ Benichou I, Givli S (2011) Applied Physics Letters 98, 091904: The Hidden Ingenuity in Titin Structure [Peer Reviewed Journal] The American Institue of Physics. [ONLINE] Available at http://apl.aip.org.libproxy.ncl.ac.uk/resource/1/applab/v98/i9/p091904_s1 [Accessed 29 November 2012].
  3. ↑ Granzier H.L., Labeit S (2004) Circulation Research 94: page 284-295: The Giant Protein Titin, American Heart Association. [ONLINE] Available at http://circres.ahajournals.org/content/94/3/284.full [Accessed 29 November 2012].
  4. ↑ The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.Bang ML et al. http://www.ncbi.nlm.nih.gov/pubmed/11717165
  5. ↑ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular Biology of The Cell, page 1028, 5th edition, New York: Garland Science.
  6. ↑ Erickson, H.P. (1997) Science, Volume 276 No 5315, page 1090-1092 Stretching Single Protein Molecules: Titin is a Weird Spring [Peer Reviewed Journal]. [ONLINE] Available at http://www.sciencemag.org.libproxy.ncl.ac.uk/content/276/5315/1090 [Accessed 29 November 2012].
  7. ↑ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular Biology of The Cell, page 1028, 5th edition, New York: Garland Science.
  8. ↑ TIBIAL MUSCULAR DYSTROPHY, TARDIVE. http://omim.org/entry/600334
  9. ↑ Muscular dystrophy with separate clinical phenotypes in a large family. Udd B et al. http://www.ncbi.nlm.nih.gov/pubmed/1745277
  10. ↑ https://www.ncbi.nlm.nih.gov/gene/7273
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