Effects of Destruxin A on Silkworm’s Immunophilins

Destruxin A (DA), a major secondary metabolite of <i>Metarhizium anisopliae</i>, has anti-immunity to insects. However, the detailed mechanism and its interactions with target proteins are elusive. Previously, three immunophilins, peptidyl&#8722;prolyl cis&#8722;trans isomerase (...

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Main Authors: Jingjing Wang, Qunfang Weng, Qiongbo Hu
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/11/6/349
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author Jingjing Wang
Qunfang Weng
Qiongbo Hu
author_facet Jingjing Wang
Qunfang Weng
Qiongbo Hu
author_sort Jingjing Wang
collection DOAJ
description Destruxin A (DA), a major secondary metabolite of <i>Metarhizium anisopliae</i>, has anti-immunity to insects. However, the detailed mechanism and its interactions with target proteins are elusive. Previously, three immunophilins, peptidyl&#8722;prolyl cis&#8722;trans isomerase (BmPPI), FK506 binding-protein 45 (BmFKBP45) and BmFKBP59 homologue, were isolated from the silkworm, <i>Bombyx mori</i> Bm12 cell line following treatment with DA, which suggested that these proteins were possible DA-binding proteins. To validate the interaction between DA and the three immunophilins, we performed bio-layer interferometry (BLI) assay, and the results showed that DA has interaction with BmPPI, whose affinity constant value is 1.98 &#215; 10<sup>&#8722;3</sup> M and which has no affinity with FKBP45 and FKBP59 homologue in vitro. Furthermore, we investigated the affinity between DA and human PPI protein (HsPPIA) and the affinity constant (K<sub>D</sub>) value is 2.22 &#215; 10<sup>&#8722;3</sup> M. Additionally, we compared the effects of silkworm and human PPI proteins produced by DA and immunosuppressants, cyclosporine A (CsA), and tacrolimus (FK506), by employing I2H (insect two-hybrid) in the SF-9 cell line. The results indicated that in silkworm, the effects created by DA and CsA were stronger than FK506. Furthermore, the effects created by DA in silkworm were stronger than those in humans. This study will offer new thinking to elucidate the molecular mechanism of DA in the immunity system of insects.
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spelling doaj.art-83eca417ddba41999bf2d3cd4e148e482022-12-22T04:03:57ZengMDPI AGToxins2072-66512019-06-0111634910.3390/toxins11060349toxins11060349Effects of Destruxin A on Silkworm’s ImmunophilinsJingjing Wang0Qunfang Weng1Qiongbo Hu2Key Laboratory of Natural Pesticide &amp; Chemical Biology, Ministry of Education; College of Agriculture, South China Agricultural University, Guangzhou 510642, ChinaKey Laboratory of Natural Pesticide &amp; Chemical Biology, Ministry of Education; College of Agriculture, South China Agricultural University, Guangzhou 510642, ChinaKey Laboratory of Natural Pesticide &amp; Chemical Biology, Ministry of Education; College of Agriculture, South China Agricultural University, Guangzhou 510642, ChinaDestruxin A (DA), a major secondary metabolite of <i>Metarhizium anisopliae</i>, has anti-immunity to insects. However, the detailed mechanism and its interactions with target proteins are elusive. Previously, three immunophilins, peptidyl&#8722;prolyl cis&#8722;trans isomerase (BmPPI), FK506 binding-protein 45 (BmFKBP45) and BmFKBP59 homologue, were isolated from the silkworm, <i>Bombyx mori</i> Bm12 cell line following treatment with DA, which suggested that these proteins were possible DA-binding proteins. To validate the interaction between DA and the three immunophilins, we performed bio-layer interferometry (BLI) assay, and the results showed that DA has interaction with BmPPI, whose affinity constant value is 1.98 &#215; 10<sup>&#8722;3</sup> M and which has no affinity with FKBP45 and FKBP59 homologue in vitro. Furthermore, we investigated the affinity between DA and human PPI protein (HsPPIA) and the affinity constant (K<sub>D</sub>) value is 2.22 &#215; 10<sup>&#8722;3</sup> M. Additionally, we compared the effects of silkworm and human PPI proteins produced by DA and immunosuppressants, cyclosporine A (CsA), and tacrolimus (FK506), by employing I2H (insect two-hybrid) in the SF-9 cell line. The results indicated that in silkworm, the effects created by DA and CsA were stronger than FK506. Furthermore, the effects created by DA in silkworm were stronger than those in humans. This study will offer new thinking to elucidate the molecular mechanism of DA in the immunity system of insects.https://www.mdpi.com/2072-6651/11/6/349Destruxin Apeptidyl-prolyl isomeraseFK506 binding proteincyclosporine AFK506<i>Bombyx mori</i>
spellingShingle Jingjing Wang
Qunfang Weng
Qiongbo Hu
Effects of Destruxin A on Silkworm’s Immunophilins
Toxins
Destruxin A
peptidyl-prolyl isomerase
FK506 binding protein
cyclosporine A
FK506
<i>Bombyx mori</i>
title Effects of Destruxin A on Silkworm’s Immunophilins
title_full Effects of Destruxin A on Silkworm’s Immunophilins
title_fullStr Effects of Destruxin A on Silkworm’s Immunophilins
title_full_unstemmed Effects of Destruxin A on Silkworm’s Immunophilins
title_short Effects of Destruxin A on Silkworm’s Immunophilins
title_sort effects of destruxin a on silkworm s immunophilins
topic Destruxin A
peptidyl-prolyl isomerase
FK506 binding protein
cyclosporine A
FK506
<i>Bombyx mori</i>
url https://www.mdpi.com/2072-6651/11/6/349
work_keys_str_mv AT jingjingwang effectsofdestruxinaonsilkwormsimmunophilins
AT qunfangweng effectsofdestruxinaonsilkwormsimmunophilins
AT qiongbohu effectsofdestruxinaonsilkwormsimmunophilins