Structural insight and stability of TNFR-Fc fusion protein (Etanercept) produced by using transgenic silkworms.

Autor: Kiyoshi M; Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan., Tatematsu KI; Transgenic Silkworm Research Unit, National Institute of Agrobiological Sciences National Agriculture and Food Research Organization, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan., Tada M; Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan., Sezutsu H; Transgenic Silkworm Research Unit, National Institute of Agrobiological Sciences National Agriculture and Food Research Organization, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan., Shibata H; Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan., Ishii-Watabe A; Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
Jazyk: angličtina
Zdroj: Journal of biochemistry [J Biochem] 2021 Feb 06; Vol. 169 (1), pp. 25-33.
DOI: 10.1093/jb/mvaa092
Abstrakt: Therapeutic proteins expressed using transgenic animals have been of great interest for several years. Especially, transgenic silkworm has been studied intensively because of its ease in handling, low-cost, high-yield and unique glycosylation patterns. However, the physicochemical property of the therapeutic protein expressed in transgenic silkworm remains elusive. Here, we constructed an expression system for the TNFR-Fc fusion protein (Etanercept) using transgenic silkworm. The TNFR-Fc fusion protein was employed to N-glycan analysis, which revealed an increased amount of afucosylated protein. Evidence from surface plasmon resonance analysis showed that the TNFR-Fc fusion protein exhibit increased binding affinity for Fcγ receptor IIIa and FcRn compared to the commercial Etanercept, emphasizing the profit of expression system using transgenic silkworm. We have further discussed the comparison of higher order structure, thermal stability and aggregation of the TNFR-Fc fusion protein.
(© The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje