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Expression screen of TNFR1 R347A, MyD88, IRAK4 death domains in E. coli followed by purification and biophysical characterization of TNFR1 R347A death domain

Przytulski, K.; Podkowka, A.; Tomczyk, T.; Gajewska, D.; Sypien, M.; Jelen, A.; Dahate, P.; Szlachcic, A.; Bista, M.; Walczak, M.

2024-12-13 biochemistry
10.1101/2024.12.13.628329 bioRxiv
Show abstract

Death domains play a crucial role in signaling pathways related to inflammation and programmed cell death, rendering them promising targets for therapeutic interventions. However, their expression as recombinant proteins often pose challenges. Here, we present expression screening of TNFR1, IRAK4, and MyD88 death domains in E. coli, followed by the biophysical characterization of TNFR1 death domain after subsequent construct optimization. The study also discusses the influence of pH and ionic strength on TNFR1R347A stability, providing statistical models to predict optimal conditions of the buffer to achieve the highest protein stability. HighlightsO_LIOptimization of expression conditions for TNFR1R347A, MyD88, IRAK4 death domains in E. coli BL21(DE3) cells. C_LIO_LIHigh-yield production of soluble monomeric TNFR1R347A death domain. C_LI

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