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Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18
Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory targe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493575/ https://www.ncbi.nlm.nih.gov/pubmed/26148664 http://dx.doi.org/10.1038/srep11863 |
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author | Guo, Peng-Chao Dong, Zhaoming Zhao, Ping Zhang, Yan He, Huawei Tan, Xiang Zhang, Weiwei Xia, Qingyou |
author_facet | Guo, Peng-Chao Dong, Zhaoming Zhao, Ping Zhang, Yan He, Huawei Tan, Xiang Zhang, Weiwei Xia, Qingyou |
author_sort | Guo, Peng-Chao |
collection | PubMed |
description | Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development. |
format | Online Article Text |
id | pubmed-4493575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44935752015-07-09 Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 Guo, Peng-Chao Dong, Zhaoming Zhao, Ping Zhang, Yan He, Huawei Tan, Xiang Zhang, Weiwei Xia, Qingyou Sci Rep Article Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development. Nature Publishing Group 2015-07-07 /pmc/articles/PMC4493575/ /pubmed/26148664 http://dx.doi.org/10.1038/srep11863 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Guo, Peng-Chao Dong, Zhaoming Zhao, Ping Zhang, Yan He, Huawei Tan, Xiang Zhang, Weiwei Xia, Qingyou Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
title | Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
title_full | Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
title_fullStr | Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
title_full_unstemmed | Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
title_short | Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
title_sort | structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493575/ https://www.ncbi.nlm.nih.gov/pubmed/26148664 http://dx.doi.org/10.1038/srep11863 |
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