Modeling protein-protein interactions in axon initial segment to understand their potential impact on action potential initiation
Abstract
The axon initial segment (AIS) region is crucial for action potential initiation due to the presence of high-density AIS protein voltage-gated sodium channels (Naᵥ). Naᵥ channels comprise several serine residues responsible for the recruitment of Naᵥ channels into the structure of AIS through interactions with ankyrin-G (AnkG). In this study, a series of computational experiments are performed to understand the role of AIS proteins casein kinase 2 and AnkG on Naᵥ channel recruitment into the AIS. The computational simulation results using Virtual cell software indicate that Naᵥ channels with all serine sites available for phosphorylation bind to AnkG with strong affinity. At the low initial concentration of AnkG and casein kinase 2, the concentration of Naᵥ channels reduces significantly, suggesting the importance of casein kinase 2 and AnkG in the recruitment of Naᵥ channels.... [Show full abstract]
Keywords
Alzheimer’s disease; ankyrin-G; axon initial segment; casein kinase-2; microtubules; voltage-gated potassium channel; voltage-gated sodium channel; Alzheimer's diseaseFields of Research
080110 Simulation and Modelling; 030402 Biomolecular Modelling and Design; 110904 Neurology and Neuromuscular Diseases; 080108 Neural, Evolutionary and Fuzzy Computation; 1109 NeurosciencesDate
2021-04Type
Journal ArticleCollections
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