Posttranslational Acetylation of α-Tubulin Constrains Protofilament Number in Native Microtubules
| Autor: | Kerwyn Casey Huang, Miriam B. Goodman, Juan G. Cueva, Jen Hsin |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Lysine Mutant Molecular Dynamics Simulation Microtubules General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Molecular dynamics 0302 clinical medicine Microtubule Tubulin Animals Caenorhabditis elegans Caenorhabditis elegans Proteins 030304 developmental biology 0303 health sciences biology Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Acetylation biology.organism_classification Cell biology Microscopy Electron Sensory dendrite biology.protein General Agricultural and Biological Sciences Mechanoreceptors Protein Processing Post-Translational 030217 neurology & neurosurgery |
| Zdroj: | Current Biology. 22(12):1066-1074 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2012.05.012 |
| Popis: | Summary Background Microtubules are built from linear polymers of α-β tubulin dimers (protofilaments) that form a tubular quinary structure. Microtubules assembled from purified tubulin in vitro contain between 10 and 16 protofilaments; however, such structural polymorphisms are not found in cells. This discrepancy implies that factors other than tubulin constrain microtubule protofilament number, but the nature of these constraints is unknown. Results Here, we show that acetylation of MEC-12 α-tubulin constrains protofilament number in C. elegans touch receptor neurons (TRNs). Whereas the sensory dendrite of wild-type TRNs is packed with a cross-linked bundle of long, 15-protofilament microtubules, mec-17;atat-2 mutants lacking α-tubulin acetyltransferase activity have short microtubules, rampant lattice defects, and variable protofilament number both between and within microtubules. All-atom molecular dynamics simulations suggest a model in which acetylation of lysine 40 promotes the formation of interprotofilament salt bridges, stabilizing lateral interactions between protofilaments and constraining quinary structure to produce stable, structurally uniform microtubules in vivo. Conclusions Acetylation of α-tubulin is an essential constraint on protofilament number in vivo. We propose a structural model in which this posttranslational modification promotes the formation of lateral salt bridges that fine-tune the association between adjacent protofilaments and enable the formation of uniform microtubule populations in vivo. |
| Databáze: | OpenAIRE |
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