A newly proposed mechanism for arginine-assisted protein refolding--not inhibiting soluble oligomers although promoting a correct structure.
Arginine has been demonstrated to be capable of suppressing aggregation during protein refolding. However, the pathway and the mechanism for arginine to participate in and to assist refolding process still remains unclear. In this study, arginine-assisted refolding of recombinant consensus interferon (rIFN-con1) was investigated. It was found that although arginine minimized the formation of protein precipitate, it failed to prevent the formation of the soluble oligomeric species. The amount of the oligomers increased with the increase in arginine concentration. This phenomenon has not been reported. On the other hand, arginine was able to promote the yield of correctly refolded rIFN-con1, which was more than 2 times higher than that in the absence of arginine. A proposed mechanism is the stabilization of different soluble species by arginine, which slowed down the conformational movement. The stabilization effect on native-like structure formation overwhelmed the oligomeric promotion effect, which resulted in a composite effect of increased refolding yield for rIFN-con1 when arginine concentration was below 0.5M.
Liu
Yong-Dong
YD
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, PR China.
Li
Jing-Jing
JJ
Wang
Fang-wei
FW
Chen
Jing
J
Li
Peng
P
Su
Zhi-Guo
ZG
D001120:Arginine / Q000737:chemistry* / Q000494:pharmacology; D002479:Inclusion Bodies / Q000187:drug effects; D007370:Interferon Type I / Q000737:chemistry*; D016898:Interferon-alpha; D011487:Protein Conformation; D017510:Protein Folding; D020673:Protein Renaturation / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D011994:Recombinant Proteins
D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; C050739:interferon alfacon-1; D001120:Arginine