4PK3

tubulin acetyltransferase complex with bisubstrate analog

Summary for 4PK3

• Entry DOI: 10.2210/pdb4pk3/pdb
• Descriptor: Alpha-tubulin N-acetyltransferase 1, ACETYL-SER-ASP-(N-ACETYL-LYS)-THR-NH2 PEPTIDE, COENZYME A, ... (4 entities in total)
• Functional Keywords: tubulin, acetyltransferase, bisubstrate, coa, transferase-peptide complex, transferase/peptide
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 24027.16

Authors

Szyk, A.,Roll-Mecak, A. (deposition date: 2014-05-13, release date: 2014-08-13, Last modification date: 2023-11-15)

Primary citation

Szyk, A.,Deaconescu, A.M.,Spector, J.,Goodman, B.,Valenstein, M.L.,Ziolkowska, N.E.,Kormendi, V.,Grigorieff, N.,Roll-Mecak, A.
Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase.
Cell, 157:1405-1415, 2014

PubMed Abstract: Acetylation of α-tubulin Lys40 by tubulin acetyltransferase (TAT) is the only known posttranslational modification in the microtubule lumen. It marks stable microtubules and is required for polarity establishment and directional migration. Here, we elucidate the mechanistic underpinnings for TAT activity and its preference for microtubules with slow turnover. 1.35 Å TAT cocrystal structures with bisubstrate analogs constrain TAT action to the microtubule lumen and reveal Lys40 engaged in a suboptimal active site. Assays with diverse tubulin polymers show that TAT is stimulated by microtubule interprotofilament contacts. Unexpectedly, despite the confined intraluminal location of Lys40, TAT efficiently scans the microtubule bidirectionally and acetylates stochastically without preference for ends. First-principles modeling and single-molecule measurements demonstrate that TAT catalytic activity, not constrained luminal diffusion, is rate limiting for acetylation. Thus, because of its preference for microtubules over free tubulin and its modest catalytic rate, TAT can function as a slow clock for microtubule lifetimes.

PubMed: 24906155
DOI: 10.1016/j.cell.2014.03.061

Experimental method

X-RAY DIFFRACTION (1.347 Å)