Structural basis for directional chitin biosynthesis
Wei Chen,
Peng Cao,
Yuansheng Liu,
Ailing Yu,
Dong Wang,
Lei Chen,
Rajamanikandan Sundarraj,
Zhiguang Yuchi,
Yong Gong (),
Hans Merzendorfer and
Qing Yang ()
Additional contact information
Wei Chen: Chinese Academy of Agricultural Sciences
Peng Cao: Beijing University of Technology
Yuansheng Liu: Dalian University of Technology
Ailing Yu: Chinese Academy of Agricultural Sciences
Dong Wang: Dalian University of Technology
Lei Chen: Chinese Academy of Agricultural Sciences
Rajamanikandan Sundarraj: Tianjin University
Zhiguang Yuchi: Tianjin University
Yong Gong: Chinese Academy of Sciences
Hans Merzendorfer: University of Siegen
Qing Yang: Chinese Academy of Agricultural Sciences
Nature, 2022, vol. 610, issue 7931, 402-408
Abstract:
Abstract Chitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting of N-acetylglucosamine (GlcNAc) units1. The key reactions of chitin biosynthesis are catalysed by chitin synthase2–4, 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.
Date: 2022
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DOI: 10.1038/s41586-022-05244-5
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