Atomic resolution structure of human ?-tubulin acetyltransferase bound to acetyl-CoA.

ABSTRACT: Acetylation of lysine residues is an important posttranslational modification found in all domains of life. ?-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 ?-tubulin acetyltransferases. Here, we present the structure of the human ?-tubulin acetyltransferase catalytic domain bound to its cosubstrate acetyl-CoA at 1.05 Å resolution. Compared with other lysine acetyltransferases of known structure, ?-tubulin acetyltransferase displays a relatively well-conserved cosubstrate binding pocket but is unique in its active site and putative ?-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 ?-tubulin acetyltransferases uses a reaction mechanism different from other lysine acetyltransferases characterized to date.

SUBMITTER: Taschner M 

PROVIDER: S-EPMC3511736 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature