8T42

Model of TTLL6 MTBH1-2 bound to microtubule

Summary for 8T42

• Entry DOI: 10.2210/pdb8t42/pdb
• Related: 8U3Z
• EMDB information: 41018 41090
• Descriptor: Tubulin alpha-1B chain, Tubulin beta chain, Tubulin polyglutamylase TTLL6, ... (6 entities in total)
• Functional Keywords: tubulin post-translational modifications, microtubules, ttll, ligase
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 5
• Total formula weight: 261175.76

Authors

Mahalingan, K.K.,Grotjahn, D.,Li, Y.,Lander, G.C.,Zehr, E.A.,Roll-Mecak, A. (deposition date: 2023-06-08, release date: 2024-05-08)

Primary citation

Mahalingan, K.K.,Grotjahn, D.A.,Li, Y.,Lander, G.C.,Zehr, E.A.,Roll-Mecak, A.
Structural basis for alpha-tubulin-specific and modification state-dependent glutamylation.
Nat.Chem.Biol., 2024

PubMed Abstract: Microtubules have spatiotemporally complex posttranslational modification patterns. Tubulin tyrosine ligase-like (TTLL) enzymes introduce the most prevalent modifications on α-tubulin and β-tubulin. How TTLLs specialize for specific substrate recognition and ultimately modification-pattern generation is largely unknown. TTLL6, a glutamylase implicated in ciliopathies, preferentially modifies tubulin α-tails in microtubules. Cryo-electron microscopy, kinetic analysis and single-molecule biochemistry reveal an unprecedented quadrivalent recognition that ensures simultaneous readout of microtubule geometry and posttranslational modification status. By binding to a β-tubulin subunit, TTLL6 modifies the α-tail of the longitudinally adjacent tubulin dimer. Spanning two tubulin dimers along and across protofilaments (PFs) ensures fidelity of recognition of both the α-tail and the microtubule. Moreover, TTLL6 reads out and is stimulated by glutamylation of the β-tail of the laterally adjacent tubulin dimer, mediating crosstalk between α-tail and β-tail. This positive feedback loop can generate localized microtubule glutamylation patterns. Our work uncovers general principles that generate tubulin chemical and topographic complexity.

PubMed: 38658656
DOI: 10.1038/s41589-024-01599-0

Experimental method

ELECTRON MICROSCOPY (3.6 Å)