The C-terminal tail extension of myosin 16 acts as a molten globule, including intrinsically disordered regions, and interacts with the N-terminal ankyrin
| Autor: | Andras Lukacs, András Kengyel, Elek Telek, Henriett Halász, Kristof Karadi, Beáta Bugyi, Miklós Nyitrai, József Kardos, Zsuzsanna Fekete |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
backfolding interaction
0301 basic medicine Protein Folding Dendritic spine PTMs post-translational modifications intrinsically disordered Biochemistry Protein Structure Secondary NHM neuronal tyrosine-phosphorylated adaptor for PI3K homology motif molten globule BME β-mercaptoethanol Myosin Ankyrin Protein secondary structure chemistry.chemical_classification I-TASSER Iterative Threading Assembly Refinement GuHCl guanidine hydrochloride C terminus of myosin 16 biology Chemistry Tryptophan Molten globule TCSPC time-correlated single-photon counting Signal transduction Hydrophobic and Hydrophilic Interactions PI3K phosphoinositide 3-kinase Protein Binding Research Article Ankyrins Myo16 myosin 16 Pro-rich proline-rich Myo16Ank myosin 16 ankyrin domain tryptophan fluorescence IDP intrinsically disordered protein Myosins Myo16Tail myosin 16 C-terminal tail WRC WAVE1 regulatory complex Myo16IQ myosin 16 IQ motif 03 medical and health sciences Protein Domains ANS 1-anilino-naphthalene-8 sulfonic acid myosin 16 Animals Computer Simulation Amino Acid Sequence Myo16Tail (−IQ) Myo16Tail without the IQ motif Molecular Biology Actin BeStSel Beta Structure Selection Phosphoinositide 3-kinase 030102 biochemistry & molecular biology G-actin globular actin Cell Biology Rats Intrinsically Disordered Proteins IDR intrinsically disordered region Spectrometry Fluorescence 030104 developmental biology Biophysics biology.protein |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.100716 |
| Popis: | The lesser-known unconventional myosin 16 protein is essential in proper neuronal functioning and has been implicated in cell cycle regulation. Its longer Myo16b isoform contains a C-terminal tail extension (Myo16Tail), which has been shown to play a role in the neuronal phosphoinositide 3-kinase signaling pathway. Myo16Tail mediates the actin cytoskeleton remodeling, downregulates the actin dynamics at the postsynaptic site of dendritic spines, and is involved in the organization of the presynaptic axon terminals. However, the functional and structural features of this C-terminal tail extension are not well known. Here, we report the purification and biophysical characterization of the Myo16Tail by bioinformatics, fluorescence spectroscopy, and CD. Our results revealed that the Myo16Tail is functionally active and interacts with the N-terminal ankyrin domain of myosin 16, suggesting an intramolecular binding between the C and N termini of Myo16 as an autoregulatory mechanism involving backfolding of the motor domain. In addition, the Myo16Tail possesses high structural flexibility and a solvent-exposed hydrophobic core, indicating the largely unstructured, intrinsically disordered nature of this protein region. Some secondary structure elements were also observed, indicating that the Myo16Tail likely adopts a molten globule–like structure. These structural features imply that the Myo16Tail may function as a flexible display site particularly relevant in post-translational modifications, regulatory functions such as backfolding, and phosphoinositide 3-kinase signaling. |
| Databáze: | OpenAIRE |
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