Tubulin—tyrosine ligase

Tubulin—tyrosine ligase (TTL) is an enzyme that in humans is encoded by the TTL gene. This enzyme is involved in the post-translational modification of tubulin, specifically the addition of a tyrosine residue to the C-terminal end of detyrosinated alpha-tubulin. This process is critical for the proper functioning of microtubules in the cell. Microtubules are essential components of the cytoskeleton, involved in cell shape, division, and intracellular transport. The action of TTL is reversible and plays a key role in the microtubule dynamics that are essential for cell movement and function.

Function

Tubulin—tyrosine ligase catalyzes the ATP-dependent addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin. This enzymatic activity is crucial for the regeneration of tyrosinated tubulin, thereby maintaining the pool of tyrosinated tubulin required for microtubule assembly and function. The tyrosination/detyrosination cycle is a post-translational modification that affects microtubule interactions with motor proteins and microtubule-associated proteins (MAPs), influencing cellular processes such as mitosis, intracellular transport, and cell motility.

Clinical Significance

Alterations in the activity or expression of TTL have been implicated in various diseases, including cancer. Abnormal levels of detyrosinated tubulin, due to altered TTL activity, can affect microtubule stability and function, potentially leading to disrupted cell division and cancer progression. Furthermore, the study of TTL and its role in microtubule dynamics has implications for the development of novel therapeutic strategies targeting microtubule function in disease.

Structure

The TTL enzyme is composed of several domains that contribute to its function, including a catalytic domain that is responsible for its enzymatic activity. The structure of TTL, as determined by X-ray crystallography and other biochemical methods, provides insights into its mechanism of action and its interaction with tubulin and ATP.

Evolution

Tubulin—tyrosine ligase is conserved across a wide range of eukaryotic organisms, highlighting its fundamental role in cell biology. The conservation of TTL and the tyrosination/detyrosination cycle suggests that this enzymatic activity is critical for the proper functioning of cells across different species.

See Also

• Microtubule
• Cytoskeleton
• Post-translational modification
• Protein tyrosine phosphorylation