Atomic resolution structure of human α-tubulin acetyltransferase bound to acetyl-CoA.
Acetylation of lysine residues is an important posttranslational modification found in all domains of life. α-Tubulin is specifically acetylated on lysine 40, a modification that serves to stabilize microtubules of axons and cilia. Whereas histone acetyltransferases have been extensively studied, there is no structural and mechanistic information available on α-tubulin acetyltransferases. Here, we present the structure of the human α-tubulin acetyltransferase catalytic domain bound to its cosubstrate acetyl-CoA at 1.05 Å resolution. Compared with other lysine acetyltransferases of known structure, α-tubulin acetyltransferase displays a relatively well-conserved cosubstrate binding pocket but is unique in its active site and putative α-tubulin binding site. Using acetylation assays with structure-guided mutants, we map residues important for acetyl-CoA binding, substrate binding, and catalysis. This analysis reveals a basic patch implicated in substrate binding and a conserved glutamine residue required for catalysis, demonstrating that the family of α-tubulin acetyltransferases uses a reaction mechanism different from other lysine acetyltransferases characterized to date.
Department of Structural Cell Biology,  Max Planck Institute of Biochemistry, D-82152 Martinsried,  Germany.
Michael
M
Taschner
Melanie
M
Vetter
Esben
E
Lorentzen
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; C049182:alpha-tubulin acetylase