The Human Centriolar Protein CEP135 Contains a Two-Stranded Coiled-Coil Domain Critical for Microtubule Binding
| Autor: | Natacha Olieric, Georgios N. Hatzopoulos, Paul Guichard, Jagan M. Obbineni, Pierre Gönczy, Michel O. Steinmetz, John Missimer, Sebastian H. W. Kraatz, Manuel Hilbert, Indrani Sen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Coiled coil Binding Sites Centriole Amino Acid Motifs Microtubule organizing center Biology Microtubules Cell biology 03 medical and health sciences 030104 developmental biology Tubulin Structural Biology Microtubule biology.protein Humans Basal body CEP135 Carrier Proteins Molecular Biology Protein Binding Microtubule nucleation |
| Zdroj: | Structure |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2016.06.011 |
| Popis: | Centrioles are microtubule-based structures that play important roles notably in cell division and cilium biogenesis. CEP135/Bld10p family members are evolutionarily conserved microtubule-binding proteins important for centriole formation. Here, we analyzed in detail the microtubule-binding activity of human CEP135 (HsCEP135). X-ray crystallography and small-angle X-ray scattering in combination with molecular modeling revealed that the 158 N-terminal residues of HsCEP135 (HsCEP135-N) form a parallel two-stranded coiled-coil structure. Biochemical, cryo-electron, and fluorescence microscopy analyses revealed that in vitro HsCEP135-N interacts with tubulin, protofilaments, and microtubules and induces the formation of microtubule bundles. We further identified a 13 amino acid segment spanning residues 96-108, which represents a major microtubule-binding site in HsCEP135-N. Within this segment, we identified a cluster of three lysine residues that contribute to the microtubule bundling activity of HsCEP135-N. Our results provide the first structural information on CEP135/Bld10p proteins and offer insights into their microtubule-binding mechanism. |
| Databáze: | OpenAIRE |
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