Microtubules are subject to several post-translational modifications, such as tyrosination. Tubulin Tyr ligase (TTL) catalyses the re-addition of a Tyr residue to the carboxyl terminus of detyrosinated α-tubulin, and this has several important cellular roles. Prota et al. identified various structures of TTL in complex with tubulin by X-ray crystallography. They found that TTL specifically recognizes the curved conformation of unassembled α-tubulin–β-tubulin dimers and binds tubulin adjacent to the dimer interface. The proximity of α-tubulin to the TTL active site and the observation that α-tubulin contains two C-terminal acidic residues necessary for TTL binding explain how TTL discriminates between α- and β-subunits. These structures also show why TTL cannot bind straight microtubules and thus selectively modifies unassembled tubulin. Notably, the tubulin-contacting residues are conserved among TTL orthologues. Moreover, nucleotide binding was important for the shaping of the TTL active site, suggesting that tyrosination reactions are coordinated with nucleotide exchange.
ORIGINAL RESEARCH PAPER
Prota A. E. et al. Structural basis of tubulin tyrosination by tubulin tyrosine ligase. J. Cell Biol. 200, 259–270 (2013)
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Baumann, K. Discrimination for a good cause. Nat Rev Mol Cell Biol 14, 130 (2013). https://doi.org/10.1038/nrm3538
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DOI: https://doi.org/10.1038/nrm3538