EMD-42884

Single-particle
3.6 Å
EMD-42884 Deposition: 20/11/2023
Map released: 29/05/2024
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-42884

Microtubule-TTLL6 map

EMD-42884

Single-particle
3.6 Å
EMD-42884 Deposition: 20/11/2023
Map released: 29/05/2024
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Mus musculus
Sample: TTLL6 bound to unmodified human microtubules
Raw data: EMPIAR-11798

Deposition Authors: Mahalingan KK , Grotjahn D , Li Y , Lander GC , Zehr EA , Roll-Mecak A
Structural basis for alpha-tubulin-specific and modification state-dependent glutamylation.
PUBMED: 38658656
DOI: doi:10.1038/s41589-024-01599-0
ISSN: 1552-4469
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.