Working at the tail end of tubulin

Working at the tail end of tubulin P rota et al. describe how the enzyme tubulin tyrosine ligase (TTL) specifi cally recognizes the C terminus of ␣-tubulin to modulate the behavior of microtubules. Many enzymes posttranslation-ally modify the C-terminal tails of the ␣-and ␤-tubulin subunits that form microtubules. TTL, for example , adds a tyrosine residue to the C terminus of ␣-tubulin, resulting in the formation of tyrosinated micro-tubules that are more dynamic than detyrosinated fi laments in cells. Mice lacking TTL die shortly after birth due to neuronal defects, but how TTL recognizes and modifi es ␣-but not ␤-tubulin is unclear. Prota et al. determined the crystal structure of TTL in a complex with ␣-and ␤-tubulin heterodimers. TTL bound at the interface of the ␣ and ␤ subunits and specifi cally recognized the dimer's curved conformation, explaining why TTL is unable to tyro-sinate polymerized microtubules, in which the tubulin subunits adopt a straighter confi guration. TTL's tubulin-contacting residues are well conserved, and mutating these amino acids largely abolished TTL's ability to tyrosinate ␣-tubulin and restrict neurite outgrowth in cultured neurons. This suggests that the neuronal defects of TTL knockout mice are due to the loss of tubulin tyrosination and not because TTL is required to tyrosinate any other substrates. TTL's orientation on tubulin heterodimers placed its catalytic domain near to ␣-tubulin's C-terminal tail, which bound to the enzyme's active site through two glutamate residues missing from ␤-tubulin's C terminus. Senior author Michel Steinmetz now wants to obtain the structures of other tubulin-modifying enzymes bound to their substrates in order to determine how their functions differ from TTL. B lümer et al. reveal that Rab GTPases are targeted to the correct intracellular membrane by the guanine nucleotide exchange factors (GEFs) that activate them. There are over 60 Rabs in human cells that regulate different vesicle traffi cking events by localizing to specifi c membrane compartments. In their inactive, GDP-bound form, Rabs are maintained in the cytosol by chaperones called GDP dissociation inhibitors (GDIs). When activated by specifi c GEFs, Rabs dissociate from GDIs and bind to membranes via lipid groups attached to their C termini. But how Rabs localize to particular membranes is unclear. Blümer et al. wondered whether RabGEFs might be important for targeting, as well as activating, the GTPase family. To test this idea, the researchers devised a way to inducibly mislocalize RabGEFs. When Rabex-5, a GEF that …