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- W2011794724 abstract "As a part of ubiquitin-dependent proteolytic network, F-box proteins play important roles in almost all regulations of cellular processes, including signal transduction, apoptosis, cell cycle, and cell division. F-box proteins bind various protein substrates and tag them with multiple ubiquitin molecules, which are then further recognized by proteasome for degradation. F-box protein and Skp1 protein (S-phase kinase-associated protein 1) are key components of the SCF (Skp1, Cullin, and F-box protein) ubiquitin-ligase complexes. We study the dynamic behavior of these protein complexes, which are modeled by a connected network of Markovian transmission. The dynamics of signal transmission between the F-box motif and the substrate binding domain of the system is obtained using the Perturbation-based Markovian Transmission (PMT) model, which was recently developed and has been successfully applied to the GroEL-GroES chaperone system (Lu and Liang, 2009). In our model, the initial perturbation generated by the protein-protein interaction on the F-box motif is transmitted by a Markovian process, in which the dynamics of the probability flow is followed by solving the master equation directly. We give details of the dynamics of several Skp1 and F-box protein complexes, including beta-TrCP, Skp2, and Cdc4. The signal transmission pathways from the F-box domain to the substrate binding domain are also identified. In addition, we predict a set of key residues which are important for allosteric transition based on their distinctive dynamic properties. Our predictions are consistent to biochemical observations. Our PMT model can be applied to other large systems of biomolecules for understanding their dynamic behavior and for identifying pathways of allostery. (Lu, Hsiao-Mei and Linag, Jie, “Perturbation-based Markovian Transmission Model for Probing Allosteric Dynamics of Large Macromolecular Assembling: A Study of GroEL-GroES,” PLoS Comp. Bio., 2009.)" @default.
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- W2011794724 date "2010-01-01" @default.
- W2011794724 modified "2023-09-29" @default.
- W2011794724 title "Identification of Signal Transmission Pathways in F-Box Proteins Using Perturbation-Based Markovian Transmission (PMT) Model" @default.
- W2011794724 doi "https://doi.org/10.1016/j.bpj.2009.12.2401" @default.
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