The superior folding of a RANTES analogue expressed in lactobacilli as compared to mammalian cells reveals a promising system to screen new RANTES mutants.
The superior folding of a RANTES analogue expressed in lactobacilli as compared to mammalian cells reveals a promising system to screen new RANTES mutants.
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DOI：
10.1016/j.pep.2009.06.018
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发表时间：
2009-11
影响因子：
1.6
通讯作者：
Vangelista, Luca
中科院分区：
文献类型：
--
作者：
Secchi, Massimiliano;Xu, Qiang;Lusso, Paolo;Vangelista, Luca
Development of effective topical microbicides for the prevention of HIV-1 sexual transmission represents a primary goal for the control of the AIDS pandemic. The viral co-receptor CCR5, used by the vast majority of primary HIV-1 isolates, is considered a primary target molecule. RANTES and its derivatives are the most suitable protein-based compounds to fight HIV-1 via CCR5 targeting. Yet, receptor activation should be avoided to prevent pro-inflammatory effects and possibly provide anti-inflammatory properties. C1C5 RANTES is a chemokine mutant that exhibits high anti-HIV-1 potency coupled with CCR5 antagonism. However, the need for the formation of an N-terminal intramolecular disulphide bridge between non-natural cysteine residues at position 1 and 5 represents a challenge for the correct folding of this protein in recombinant expression systems, a crucial step towards its development as a microbicide against HIV-1. We report here a rare case of superior folding in a prokaryote as compared to an eukaryotic expression system. Production of C1C5 RANTES was highly impaired in CHO cells, with a dramatic yield reduction compared to that of wild type RANTES and secretion of the molecule as disulphide-linked dimer. Conversely, a human vaginal isolate of Lactobacillus jensenii engineered to secrete C1C5 RANTES provided efficient delivery of the monomeric protein. This and other reports on successful secretion of complex proteins indicate that lactic acid bacteria are an excellent system for the expression of therapeutic proteins, which can be used as a platform for the engineering of conceptually novel RANTES mutants with potent anti-HIV-1 activity.
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影响因子：
32.4
作者：
Hladik, Florian;Sakchalathorn, Polachai;Ballweber, Lamar;Lentz, Gretchen;Fialkow, Michael;Eschenbach, David;McElrath, M. Juliana
通讯作者：
McElrath, M. Juliana
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56.3
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Cutler, Blayne;Justman, Jessica
通讯作者：
Justman, Jessica
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Liu, Xiaowen;Lagenaur, Laurel A.;Xu, Qiang
通讯作者：
Xu, Qiang
影响因子：
56.9
作者：
COCCHI, F;DEVICO, AL;LUSSO, P
通讯作者：
LUSSO, P
影响因子：
2.9
作者：
CHUNG, CW;COOKE, RM;WELLS, TNC
通讯作者：
WELLS, TNC