Small heat shock proteins protect mammalian cells from cofilinopathy
DOI:
https://doi.org/10.33910/2687-1270-2024-5-3-294-306Keywords:
neurodegenerative diseases, cell cytoskeleton, ADF/cofilins, small heat shock protein, proteinprotein docking, chaperone functionAbstract
The regulation of actin cytoskeleton dynamics is crucial for cellular function. The actin-depolymerizing factor (ADF)/cofilin family of actin-binding proteins plays a significant role in this process. Dysregulation of the interaction between neural tissue cell cytoskeletons and ADF/cofilin proteins can contribute to the development of neurodegenerative diseases. Mammals typically express three forms of ADF/cofilins: destrin, cofilin-1, and cofilin-2. Under stress conditions, small heat shock proteins (sHsp27), known for their broad specificity to target proteins, are upregulated in mammalian cells. We hypothesized that sHsp27 proteins may bind ADF/cofilins, and used the ClusPro 2.0 tool for docking simulations of these three ADF/cofilins into a 24-dimensional sHsp27 protein complex. Our results revealed that cofilin-1 formed the strongest interaction with sHsp27, followed by destrin and cofilin-2. Notably, cofilin-1 modulates the remodeling of F-actin, a key cytoskeletal protein involved in dendritic spine formation and synaptic plasticity. Thus, sHsp27 may serve as a chaperone for ADF/cofilins, protecting cells from their harmful accumulation.
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