Titin

Titin
	Structure according to PDB 1bpv
	Existing structure data: 1bpv , 1g1c , 1h8b , 1nct , 1ncu , 1tit , 1tiu , 1tki , 1tnm , 1tnn , 1waa , 1ya5 , 2a38 , 2bk8 , 2f8v , 2ill , 2nzi , 3lpw , 3puc , 3q5o , 3qp3 , 3knb
Properties of human protein
Mass / length primary structure	34350 aa
Isoforms	8th
Identifier
Gene name	TTN
External IDs	OMIM : 188840 ; MGI : 98864 ;
Enzyme classification
EC, category	2.7.11.1 , transferases
Occurrence
Parent taxon	Euteleostomi
	Orthologue

Proteins of the sarcomere

Titin (also connectin ) is an elastic protein that weighs around 3.6 megadaltons and is composed of filaments (protein threads). Human titin consists of approx. 34,000 amino acids and has 320 protein domains , making it the largest known human protein. It is part of the sarcomere , the smallest functional unit in the striated muscles . The job of titin in the sarcomere is to center the myosin heads between the actin filaments and to reset the contractile apparatus after stretching. Described clearly, it works like a large rubber band in our muscles.

Occurrence

The titin filament and the actin filament are mechanically connected to the Z-disk via alpha-actinin . This bond is relatively weak and easy to regulate, a necessary prerequisite for the unhindered contraction process. In addition, it binds to telethonin (T-Cap) in the area of the Z-disk . In the area of the A-band, its stiff carboxyl end is connected to the M-disk.

In the area of the I-band, the long polypeptide is elastic and can be stretched. The structure of titin differs in skeletal and cardiac muscles , which explains the lower elasticity of the cardiac sarcomere.

The titin filament is not involved in the muscle contraction , it ensures the elasticity and stability of the muscle and has a major influence on the contraction speed. In addition, the titin is responsible for the resting tension of the muscle and is therefore often mentioned in discussions about the sense or nonsense of stretching .

history

For most of the past century, the existence of titin, the largest protein in the human body, was unknown although it is the third most abundant muscle protein after myosin and actin according to current knowledge. Calculations show that it makes up 400 grams of body weight in an adult male. The theories of muscle contraction were based on the molecules known at the time, especially actin and myosin. It took several decades for the presence of titin in the sarcomere to become widely accepted.

The story of Titin began in the late 1970s. In 1977 Koscak Maruyama and co-workers isolated an elastic protein from muscle fibers that they named connectin. It turned out that this protein is larger than any known muscle protein. Paradoxically, precisely because of its size, it was overlooked for a long time: the protein has too little mobility in the usual gel electrophoresis and cannot be detected; only when you use extremely thin gels does it become visible on the gel.

Two years later, Kuan Wang and co-workers identified a doublet band on an electrophoresis gel that corresponded to a high-molecular, elastic protein they named titin.

In 1990 Siegfried Labeit isolated a partial cDNA clone of titin. In 1995 Labeit and Bernhard Kolmerer determined the cDNA sequence of the human cardiac titin and showed that isoforms of the protein exist in different muscles that differ considerably in size. For example, the cardiac titin isoform has a mass of approximately 3 MDa, while the titin of the muscular soleus has approximately 3.7 MDa. This enormous difference in size is based on different lengths of I-band titin areas of these muscles. In 2001 Labeit and colleagues determined the complete sequence of the human titin gene.

Genomics

The human gene that codes for titin is located on the long arm of chromosome 2 and contains 363 exons which together code for 38,138 residues (4200 kDa). Within the gene there is a large number of PEVK exons (proline-glutamate-valine-lysine - abundant exons) with a length of 84 to 99 nucleotides, which code for conserved 28 to 33 residual motifs, the structural units of the titin-PEVK- Can represent spring. The number of PEVK motifs in the titin gene seems to have increased in the course of evolution, which apparently changed the genomic region that is responsible for the properties of the titin feather.

literature

Franziska Rudolph, Judith Hüttemeister, Katharina da Silva Lopes, René Jüttner, Lily Yu, Nora Bergmann, Dhana Friedrich, Stephan Preibisch, Eva Wagner, Stephan E Lehnart, Carol C Gregorio, Michael Gotthardt: Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes. In: PNAS 116, 50, 2019: 25126-25136. Abstract.

Web links

Titin in the muscle

Individual evidence

↑ ProtParam: TITIN_HUMAN (Q8WZ42) , web.expasy.org, accessed on March 17, 2018.
↑ Accordingly, it was named after the titans , the giants from Greek mythology.
↑ Stefan Silbernagel, Agamemnon Despopoulos: Pocket Atlas Physiology . 8th edition. Thieme, S. 64 .
↑ Maruyama K, Matsubara S, Natori R, Nonomura Y, Kimura S: Connectin, an elastic protein of muscle. Characterization and Function . In: Journal of Biochemistry . 82, No. 2, August 1977, pp. 317-37. PMID 914784 .
↑ Wang K, McClure J, Tu A, Titin: major myofibrillar components of striated muscle, Proceedings of the National Academy of Sciences of the United States of America, volume = 76, issue = 8, pages = 3698–702, date = August 1979, pmid = 291034, pmc = 383900, doi = 10.1073 / pnas.76.8.3698
↑ Maruyama K, Connectin, an elastic protein of striated muscle, Biophysical Chemistry, 50, 1-2, pages = 73-85, May 1994, pmid = 8011942, doi = 10.1016 / 0301-4622 (94) 85021-6
↑ Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (November 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". Circulation Research. 89 (11): 1065-72. doi: 10.1161 / hh2301.100981. PMID 11717165

[TitinProtParam-1] ProtParam: TITIN_HUMAN (Q8WZ42) , web.expasy.org, accessed on March 17, 2018.

[2] Accordingly, it was named after the titans , the giants from Greek mythology.

[3] Stefan Silbernagel, Agamemnon Despopoulos: Pocket Atlas Physiology . 8th edition. Thieme, S. 64 .

[4] Maruyama K, Matsubara S, Natori R, Nonomura Y, Kimura S: Connectin, an elastic protein of muscle. Characterization and Function . In: Journal of Biochemistry . 82, No. 2, August 1977, pp. 317-37. PMID 914784 .

[5] Wang K, McClure J, Tu A, Titin: major myofibrillar components of striated muscle, Proceedings of the National Academy of Sciences of the United States of America, volume = 76, issue = 8, pages = 3698–702, date = August 1979, pmid = 291034, pmc = 383900, doi = 10.1073 / pnas.76.8.3698

[6] Maruyama K, Connectin, an elastic protein of striated muscle, Biophysical Chemistry, 50, 1-2, pages = 73-85, May 1994, pmid = 8011942, doi = 10.1016 / 0301-4622 (94) 85021-6

[7] Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (November 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". Circulation Research. 89 (11): 1065-72. doi: 10.1161 / hh2301.100981. PMID 11717165