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Structural basis for directional chitin biosynthesis
Chitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting of N-acetylglucosamine (GlcNAc) units(1). The key reactions of chitin biosynthesis are catalysed by chitin synthase(2–4), a membrane-integrated glycosyltransferase that transfers GlcNAc from UDP-GlcNAc to...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556331/ https://www.ncbi.nlm.nih.gov/pubmed/36131020 http://dx.doi.org/10.1038/s41586-022-05244-5 |
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author | Chen, Wei Cao, Peng Liu, Yuansheng Yu, Ailing Wang, Dong Chen, Lei Sundarraj, Rajamanikandan Yuchi, Zhiguang Gong, Yong Merzendorfer, Hans Yang, Qing |
author_facet | Chen, Wei Cao, Peng Liu, Yuansheng Yu, Ailing Wang, Dong Chen, Lei Sundarraj, Rajamanikandan Yuchi, Zhiguang Gong, Yong Merzendorfer, Hans Yang, Qing |
author_sort | Chen, Wei |
collection | PubMed |
description | Chitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting of N-acetylglucosamine (GlcNAc) units(1). The key reactions of chitin biosynthesis are catalysed by chitin synthase(2–4), a membrane-integrated glycosyltransferase that transfers GlcNAc from UDP-GlcNAc to a growing chitin chain. However, the precise mechanism of this process has yet to be elucidated. Here we report five cryo-electron microscopy structures of a chitin synthase from the devastating soybean root rot pathogenic oomycete Phytophthora sojae (PsChs1). They represent the apo, GlcNAc-bound, nascent chitin oligomer-bound, UDP-bound (post-synthesis) and chitin synthase inhibitor nikkomycin Z-bound states of the enzyme, providing detailed views into the multiple steps of chitin biosynthesis and its competitive inhibition. The structures reveal the chitin synthesis reaction chamber that has the substrate-binding site, the catalytic centre and the entrance to the polymer-translocating channel that allows the product polymer to be discharged. This arrangement reflects consecutive key events in chitin biosynthesis from UDP-GlcNAc binding and polymer elongation to the release of the product. We identified a swinging loop within the chitin-translocating channel, which acts as a ‘gate lock’ that prevents the substrate from leaving while directing the product polymer into the translocating channel for discharge to the extracellular side of the cell membrane. This work reveals the directional multistep mechanism of chitin biosynthesis and provides a structural basis for inhibition of chitin synthesis. |
format | Online Article Text |
id | pubmed-9556331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95563312022-10-14 Structural basis for directional chitin biosynthesis Chen, Wei Cao, Peng Liu, Yuansheng Yu, Ailing Wang, Dong Chen, Lei Sundarraj, Rajamanikandan Yuchi, Zhiguang Gong, Yong Merzendorfer, Hans Yang, Qing Nature Article Chitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting of N-acetylglucosamine (GlcNAc) units(1). The key reactions of chitin biosynthesis are catalysed by chitin synthase(2–4), a membrane-integrated glycosyltransferase that transfers GlcNAc from UDP-GlcNAc to a growing chitin chain. However, the precise mechanism of this process has yet to be elucidated. Here we report five cryo-electron microscopy structures of a chitin synthase from the devastating soybean root rot pathogenic oomycete Phytophthora sojae (PsChs1). They represent the apo, GlcNAc-bound, nascent chitin oligomer-bound, UDP-bound (post-synthesis) and chitin synthase inhibitor nikkomycin Z-bound states of the enzyme, providing detailed views into the multiple steps of chitin biosynthesis and its competitive inhibition. The structures reveal the chitin synthesis reaction chamber that has the substrate-binding site, the catalytic centre and the entrance to the polymer-translocating channel that allows the product polymer to be discharged. This arrangement reflects consecutive key events in chitin biosynthesis from UDP-GlcNAc binding and polymer elongation to the release of the product. We identified a swinging loop within the chitin-translocating channel, which acts as a ‘gate lock’ that prevents the substrate from leaving while directing the product polymer into the translocating channel for discharge to the extracellular side of the cell membrane. This work reveals the directional multistep mechanism of chitin biosynthesis and provides a structural basis for inhibition of chitin synthesis. Nature Publishing Group UK 2022-09-21 2022 /pmc/articles/PMC9556331/ /pubmed/36131020 http://dx.doi.org/10.1038/s41586-022-05244-5 Text en © The Author(s) 2022, corrected publication 2022, 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chen, Wei Cao, Peng Liu, Yuansheng Yu, Ailing Wang, Dong Chen, Lei Sundarraj, Rajamanikandan Yuchi, Zhiguang Gong, Yong Merzendorfer, Hans Yang, Qing Structural basis for directional chitin biosynthesis |
title | Structural basis for directional chitin biosynthesis |
title_full | Structural basis for directional chitin biosynthesis |
title_fullStr | Structural basis for directional chitin biosynthesis |
title_full_unstemmed | Structural basis for directional chitin biosynthesis |
title_short | Structural basis for directional chitin biosynthesis |
title_sort | structural basis for directional chitin biosynthesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556331/ https://www.ncbi.nlm.nih.gov/pubmed/36131020 http://dx.doi.org/10.1038/s41586-022-05244-5 |
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