α-Tubulin acetylation from the inside out

Abstract

Posttranslational modification of proteins, including phosphorylation, ubiquitylation, and acetylation, is an important means of signaling and functional specialization in the cell. The acetylation of lysine residues is best understood in histone proteins, in which histone acetyltransferases modify histone tail sequences to regulate chromatin structure. However, lysine acetylation has recently become more appreciated as a widely distributed phenomenon regulating diverse proteins and cellular systems (1). One such system is the microtubule (MT) cytoskeleton. MTs are highly dynamic tubular polymers assembled from protofilaments of α/β-tubulin dimers, and are essential for intracellular transport, architectural organization, and force production in eukaryotic cells (2). Acetylation of the conserved lysine 40 (K40) residue of α-tubulin, first reported more than 25 y ago (3), is one of several conserved posttranslational modifications found in the tubulin protein (2, 3). Although MTs generally function as highly dynamic polymers, α-tubulin K40 acetylation is associated with unusually stable MTs. These act as tracks for organelle and macromolecule transport in neurons, and form the structural scaffolds, called axonemes, at the core of beating cilia and flagella (4, 5). α-Tubulin K40 acetylation is catalyzed by a conserved α-tubulin acetyltransferase (α-TAT), but neither the detailed mechanism of tubulin acetylation nor its downstream functional consequences are well understood (6, 7). Now, in parallel studies presented in PNAS, Friedmann et al. (8) and Taschner et al. (9) describe the 3D structure of human α-TAT and the chemical basis for α-tubulin K40 acetylation. The two studies show how α-TAT selectively acetylates α-tubulin K40 and explore α-TAT’s catalytic mechanism through detailed enzymatic analysis (8, 9).