Titin
Template:PBB Titin, also known as connectin, is the largest known protein that is important in the contraction of striated muscle tissues.[1][2]
Structure
Titin is the largest known protein, consisting of 34,350 amino acids. The molecular weight of the mature protein is approximately 2,993,442.763 Da,[3] and it has a theoretical isoelectric point of 6.01.[4] The protein's empirical chemical formula is C132983H211861N36149O40883S693. It has a theoretical instability index (II) of 39.69, indicating that it would be stable in a test tube. The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to disappear after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes).[5]
Function
Titin is a large abundant protein of striated muscle. The protein is divided into two regions:
- N-terminal I-band
- is the elastic part of the molecule, contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine and lysine
- C-terminal A-band
- thought to act as a protein-ruler, contains a mixture of immunoglobulin and fibronectin repeats, and possesses kinase activity.
A N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere respectively so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Of the many titin variants identified, five for which complete transcript information is available are described.[2][6]
Titin interacts with many sarcomeric proteins including:[7]
- Z line region: telethonin and alpha-actinin
- I band region: calpain-3 and obscurin
- M line region: myosin-binding protein C, calmodulin 1, CAPN3, and MURF1
Clinical relevance
Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9[8][9] and tibial muscular dystrophy.[10] Autoantibodies to titin are produced in patients with the autoimmune disease scleroderma.[11]
Linguistic significance
As the largest known protein, titin also has the longest IUPAC name. The full chemical name, which starts Methionyl... and ends ...isoleucine, contains 189,819 letters and is sometimes stated to be the longest word in the English language, or any language.[12] However, professional dictionary writers regard generic names of chemical compounds as verbal formulae rather than English words.[13]
Additional images
-
Sliding filament model of muscle contraction. (Titin labeled at upper right.)
References
- ^ Online Mendelian Inheritance in Man (OMIM): 188840
- ^ a b "Entrez Gene: TTN titin".
- ^ Result of Molecular Weight Calculation
- ^ "ExPASy-calculated pI for titin". Retrieved 2007-08-26.
- ^ "Swiss-Prot Protein knowledgebase, main entry". Retrieved 2006-05-04.
- ^ Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A, Trinick J (1990). "A regular pattern of two types of 100-residue motif in the sequence of titin". Nature. 345 (6272): 273–6. doi:10.1038/26926a0. PMID 2129545.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (2001). "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". Circ. Res. 89 (11): 1065–72. doi:10.1161/hh2301.100981. PMID 11717165.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Siu BL, Niimura H, Osborne JA, Fatkin D, MacRae C, Solomon S, Benson DW, Seidman JG, Seidman CE (1999). "Familial dilated cardiomyopathy locus maps to chromosome 2q31". Circulation. 99 (8): 1022–6. PMID 10051295.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Itoh-Satoh M, Hayashi T, Nishi H, Koga Y, Arimura T, Koyanagi T, Takahashi M, Hohda S, Ueda K, Nouchi T, Hiroe M, Marumo F, Imaizumi T, Yasunami M, Kimura A (2002). "Titin mutations as the molecular basis for dilated cardiomyopathy". Biochem. Biophys. Res. Commun. 291 (2): 385–93. doi:10.1006/bbrc.2002.6448. PMID 11846417.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B (2002). "Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin". Am. J. Hum. Genet. 71 (3): 492–500. doi:10.1086/342380. PMC 379188. PMID 12145747.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Machado C, Sunkel CE, Andrew DJ (1998). "Human autoantibodies reveal titin as a chromosomal protein". J. Cell Biol. 141 (2): 321–33. doi:10.1083/jcb.141.2.321. PMC 2148454. PMID 9548712.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ "What is the longest word in the English language?". CliffsNotes.com. Retrieved 2009-05-26.
- ^ Oxford Word and Language Service team. "Ask the experts - What is the longest English word?". AskOxford.com / Oxford University Press. Retrieved 2008-01-13.
Further reading
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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