4pk3 | pdb_00004pk3
tubulin acetyltransferase complex with bisubstrate analog
Structural highlights
Function[ATAT_HUMAN] Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. May affect microtubule stability and regulate microtubule dynamics. May be involved in neuron development.[1] Publication Abstract from PubMedAcetylation of alpha-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 A 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. Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase.,Szyk A, Deaconescu AM, Spector J, Goodman B, Valenstein ML, Ziolkowska NE, Kormendi V, Grigorieff N, Roll-Mecak A Cell. 2014 Jun 5;157(6):1405-15. doi: 10.1016/j.cell.2014.03.061. PMID:24906155[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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