Tubulin tyrosine ligase

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Function

Tubulin tyrosine ligase (TTL) adds tyrosine in an ATP-dependent reaction to the C-terminal of a detyrosinated a-tubulin. The detyrosination of α-tubulin is a posttranslational modification which exposes glutamate in the new tubulin C-terminal. The detyrosinated α-tubulin forms Glu-microtubules[1]. The complex of TTL and tubulin contains Stathmin (STM) - another tubulin-binding protein[2].

Disease

Mutated TTL causes morphogenic abnormalities and cancer. There is a loss of TTL activity during tumor growth[3].

Structural highlights

. TTL structure is composed of . via 3 loops and one helix terminal[4].

3D Structures of tubulin tyrosine ligase

Tubulin tyrosine ligase 3D structures

References

  1. ↑ Idriss HT. Phosphorylation of tubulin tyrosine ligase: a potential mechanism for regulation of alpha-tubulin tyrosination. Cell Motil Cytoskeleton. 2000 May;46(1):1-5. PMID:10842328 doi:<1::AID-CM1>3.0.CO;2-6 http://dx.doi.org/10.1002/(SICI)1097-0169(200005)46:1<1::AID-CM1>3.0.CO;2-6
  2. ↑ Szyk A, Piszczek G, Roll-Mecak A. Tubulin tyrosine ligase and stathmin compete for tubulin binding in vitro. J Mol Biol. 2013 Jul 24;425(14):2412-4. doi: 10.1016/j.jmb.2013.04.017. Epub 2013, Apr 25. PMID:23624152 doi:http://dx.doi.org/10.1016/j.jmb.2013.04.017
  3. ↑ Lafanechere L, Courtay-Cahen C, Kawakami T, Jacrot M, Rudiger M, Wehland J, Job D, Margolis RL. Suppression of tubulin tyrosine ligase during tumor growth. J Cell Sci. 1998 Jan;111 ( Pt 2):171-81. PMID:9405300
  4. ↑ Prota AE, Magiera MM, Kuijpers M, Bargsten K, Frey D, Wieser M, Jaussi R, Hoogenraad CC, Kammerer RA, Janke C, Steinmetz MO. Structural basis of tubulin tyrosination by tubulin tyrosine ligase. J Cell Biol. 2013 Feb 4;200(3):259-70. doi: 10.1083/jcb.201211017. Epub 2013 Jan , 28. PMID:23358242 doi:http://dx.doi.org/10.1083/jcb.201211017

Tubulin tyrosine ligase (cyan) complex with α-tubulin (grey and pink), β-tubulin (green and yellow), stathmin (magenta), MES, GTP, Ca+2, Cl- and Mg+2 ions (PDB code 4iij)

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Michal Harel, Alexander Berchansky, Joel L. Sussman
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