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Structural basis for directional chitin biosynthesis.

<div class='caption-title'>The apo PsChs1 structure.</div>
<div class='caption-title'>Interface interactions within a PsChs1 dimer.</div>
<div class='caption-title'>Interactions between PsChs1 and ligands.</div>
Chen W, Cao P, Liu Y, Yu A, Wang D, Chen L, Sundarraj R, Yuchi Z, Gong Y, Merzendorfer H, Yang Q
OpenAccess logo Nature (2022)
Related entries: 7wjm, 7wjn, 7wjo, 7x05

Cited: 17 times
EuropePMC logo PMID: 36131020

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.

Reviews citing this publication (4)

  1. Chitin Biosynthesis in Aspergillus Species. Brauer VS, Pessoni AM, Freitas MS, Cavalcanti-Neto MP, Ries LNA, Almeida F. J Fungi (Basel) 9 89 (2023)
  2. Catalytically Active Carbon for Oxygen Reduction Reaction in Energy Conversion: Recent Advances and Future Perspectives. Liu S, Wang A, Liu Y, Zhou W, Wen H, Zhang H, Sun K, Li S, Zhou J, Wang Y, Jiang J, Li B. Adv Sci (Weinh) 11 e2308040 (2024)
  3. Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights. Zhou Y, Reynolds TB. J Fungi (Basel) 10 171 (2024)
  4. Late-stage diversification of bacterial natural products through biocatalysis. Lazic J, Filipovic V, Pantelic L, Milovanovic J, Vojnovic S, Nikodinovic-Runic J. Front Bioeng Biotechnol 12 1351583 (2024)

Articles citing this publication (13)

  1. Insights into substrate coordination and glycosyl transfer of poplar cellulose synthase-8. Verma P, Kwansa AL, Ho R, Yingling YG, Zimmer J. Structure 31 1166-1173.e6 (2023)
  2. Structure, catalysis, chitin transport, and selective inhibition of chitin synthase. Chen DD, Wang ZB, Wang LX, Zhao P, Yun CH, Bai L. Nat Commun 14 4776 (2023)
  3. Comparative Transcriptome Analysis Unravels the Response Mechanisms of Fusarium oxysporum f.sp. cubense to a Biocontrol Agent, Pseudomonas aeruginosa Gxun-2. Li S, Ma J, Li S, Chen F, Song C, Zhang H, Jiang M, Shen N. Int J Mol Sci 23 15432 (2022)
  4. Unexpected Distribution of Chitin and Chitin Synthase across Soft-Bodied Cnidarians. Vandepas LE, Tassia MG, Halanych KM, Amemiya CT. Biomolecules 13 777 (2023)
  5. A dynamic interplay between chitin synthase and the proteins Expansion/Rebuf reveals that chitin polymerisation and translocation are uncoupled in Drosophila. De Giorgio E, Giannios P, Espinàs ML, Llimargas M. PLoS Biol 21 e3001978 (2023)
  6. Customized chitooligosaccharide production-controlling their length via engineering of rhizobial chitin synthases and the choice of expression system. Weyer R, Hellmann MJ, Hamer-Timmermann SN, Singh R, Moerschbacher BM. Front Bioeng Biotechnol 10 1073447 (2022)
  7. Enzymes in 3D: Synthesis, remodelling, and hydrolysis of cell wall (1,3;1,4)-β-glucans. Hrmova M, Zimmer J, Bulone V, Fincher GB. Plant Physiol 194 33-50 (2023)
  8. Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens. Sedzicki J, Ni D, Lehmann F, Stahlberg H, Dehio C. Nat Commun 15 1844 (2024)
  9. Dynamic microvilli sculpt bristles at nanometric scale. Ikeda KN, Belevich I, Zelaya-Lainez L, Orel L, Füssl J, Gumulec J, Hellmich C, Jokitalo E, Raible F. Nat Commun 15 3733 (2024)
  10. Effect of chitin-architected spatiotemporal three-dimensional culture microenvironments on human umbilical cord-derived mesenchymal stem cells. Zhu S, Xuan J, Shentu Y, Kida K, Kobayashi M, Wang W, Ono M, Chang D. Bioact Mater 35 291-305 (2024)
  11. Modulation of host lipid metabolism by virus infection leads to exoskeleton damage in shrimp. Wang XX, Ding MJ, Gao J, Zhao L, Cao R, Wang XW. PLoS Pathog 20 e1012228 (2024)
  12. Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight. Ran Y, Shehzadi K, Liang JH, Yu MJ. Int J Mol Sci 25 3512 (2024)
  13. The N-terminal disordered region of ChsB regulates its efficient transport to the hyphal apical surface in Aspergillus nidulans. Jin J, Iwama R, Horiuchi H. Curr Genet 69 175-188 (2023)


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