Titin,also known as connectin, is a flexible intrasarcomeric filamentous protein, which is largest proteins known today.[1] Titins are a family of large proteins that which can be broken down into two subclasses of striated and non-muscle cells of vertebrates [1].
Overall Structure
Titin, a polypeptide chain protein that is greater than 1µm in length and 3-4 nm in width [2]. The protein molecule has a molecular weight of up to approximately 4 Mda. Titin is a multi-domain structure that which is found to be composed of two types of domains similar to immunoglobulin (Ig) and fibronectin.[3] There are approximately 300 Ig and fibronectin domains present in titin, with also kinase domains close to the carboxyl terminus.[2] These two types of domains are β-sandwiches of seven or eight strands that are made of about 100 residues.[2] The carboxyl terminus is in the head region of a titin molecule, the carboxyl terminus is represented as the red part molecule image.[2] The structure also contains specialized binding sites and a putative elastic region, the PEVK domain, and there is a unique sequence region part of a titin molecule [3]. Titin being amulti-domain structure is evident by the interdomain periodicity seen in the structure.[2] A titin molecule is half a sacromeres size with the four regions of the I-band,the A-band, the M-line and the Z-line. [2] The I-band section of the titin is made up of only Ig domains and unique sequences with the Ig domains arranged in tandem.[2] The A-band section is the largest part of the protein molecule with a highly conserved sequence.[2] In the A-band section the Ig and fibronectin domains are set up in a long range pattern and are called the super repeats. There are two types of the Ig and fibronectin sets that are arranged in long range patterns, made from either seven and eleven domains. Located near the end of the A-band there are six copies of small super repeats, that which are 25-30 nm long. [2] The M-line contains the overlapped carboxyl terminus regions of the titin molecule. [2] The Z-line region is on the opposite end which has the overlapped amino terminal regions of a molecule from the neighboring sacromere.[2]
Function
Titin seems to be a key component in the assembly and functioning of vertebrates straited muscles.[2] A primary function of titin is giving elastic stabilization of relative positions of myosin and actin filaments.[2] It has regions that mirror the different parts of the sacromere, which have mechanical functions, catalytic functions and the ability to bind many other sacromere proteins. [2] The protein molecules plays a role in thick-filament and sacromere assembly.[2] Titin has a role in muscle signalling mechanisms, this was discovered from the kinase domain toward the carboxy-terminal, M-line end, and potential phosphorylation sites near both ends.[2] It is known that both the Z-line and M-line ends of the titin molecules are parts of the signalling pathway that control tension and protein-turnover-related mechanisms.[2] Titin is also responsible for the elasticity of relaxed striated muscles and acts as the molecular scaffold for thick filament formation.[2] It generates most of the elastic response of a sacromere, which responds like a bidirectional spring which stretches and recoils during movement of muscles to cause the myofibril to go back to its resting state [4]. In mature muscle, titin molecules is to take part in the mechanisms that control elasticity and the operating range (the length range of sacromeres when they shorten and extend in muscle in vivo) of sacromere lengths and tension-related processes in the body. [2]
Titin that is intact has been found to be important for normal muscle structure and function.[2] This was observed when titin mutation disrupted the sacromere assembly and function, an example would be mutations that affect the I-band portion of titin would change the elasticity of muscle.[2]
Titin linked with chromosomes, having a key role in mitosis.[1] During mitosis, titin control the axial diameter of mitotic chromosomes.[1]
Structure Related to Function
Titin is a fairly linear protein with a reasoning to why the structure is that way. Titin being a filamentous shaped protein is able to its job in striated muscles.[1] The molecules are formed with bands themselves and when they form sacromeres they line up next to one another in a linear fashion. The structure is able to give an idea on how it relates to the function and how titin works as an elastic in muscles.
- ↑ 1.0 1.1 1.2 1.3 1.4 Trinick J, Tskhovrebova L. Titin: a molecular control freak. Trends Cell Biol. 1999 Oct;9(10):377-80. PMID:10481174
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 Tskhovrebova L, Trinick J. Titin: properties and family relationships. Nat Rev Mol Cell Biol. 2003 Sep;4(9):679-89. PMID:14506471 doi:10.1038/nrm1198
- ↑ 3.0 3.1 Tskhovrebova L, Trinick J, Sleep JA, Simmons RM. Elasticity and unfolding of single molecules of the giant muscle protein titin. Nature. 1997 May 15;387(6630):308-12. PMID:9153398 doi:10.1038/387308a0
- ↑ von Castelmur E, Marino M, Svergun DI, Kreplak L, Ucurum-Fotiadis Z, Konarev PV, Urzhumtsev A, Labeit D, Labeit S, Mayans O. A regular pattern of Ig super-motifs defines segmental flexibility as the elastic mechanism of the titin chain. Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1186-91. Epub 2008 Jan 22. PMID:18212128
