Cited by 3Advanced Electron Microscopy Techniques and ApplicationsEnzyme Structure and FunctionProtein Structure and Dynamics

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Absolute hand determination of glycofibrils from natural sources in cryo-EM

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Zhang, Qi, Qin, Lanju, Wang, Tongtong, Li, Zhangqiang, Zhang, Yilin, Chen, Sheng, Ge, Qijun, Wen, Jialing, Yan, Nieng, Wang, Jiawei, Hu, Mingxu·2026·Proceedings of the National Academy of Sciences

Published version of a preprint

Abstract

Glycans are not only one of the four fundamental macromolecular classes that constitute life, but also the most abundant among these four across the Earth. However, compared with proteins and nucleic acids, our understanding of the structures and functional mechanisms of glycans remains limited. Moreover, it is generally challenging to obtain high-resolution three-dimensional structures of glycans. Recent studies have demonstrated the potential of the CryoSeek strategy in enabling high-throughput structural determination of glycans, thereby presenting novel avenues for their structural investigation. Meanwhile, unlike proteins, near atomic resolution density maps of glycofibrils do not inherently facilitate the determination of absolute hand, which is a prerequisite for building atomic models of glycofibrils. Existing absolute hand determination methods have severe limitations in the case of glycofibrils from natural sources. In this study, we introduce Ahaha, a straightforward and efficient method for determining such absolute hand in cryogenic electron microscopy. With their absolute hand measured by Ahaha, we built atomic models of four glycofibrils derived from a natural water sample, facilitating the study of glycans. The online service of Ahaha is available at https://cryoseek.org/ahaha .

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Metadata

Authors
Zhang, Q., Qin, L., Wang, T., Li, Z., Zhang, Y., Chen, S., Ge, Q., Wen, J., Yan, N., Wang, J., & Hu, M.
Affiliations
  • Shenzhen Medical Academy of Research and Translation (CN)
  • Institute of Bio-Architecture and Bio-Interactions
  • Center for Life Sciences (CN)
Corresponding author
  • Yan, Nieng
  • Wang, Jiawei
  • Hu, Mingxu
Venue
Proceedings of the National Academy of Sciences
Published
2026-02-25
Volume
123
Issue
9
Pages
e2531477123-e2531477123
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W7131404605
Cited by
3
References
1
Citations by year
2026: 3
FWCI
5.90
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
Funders
MOST | National Natural Science Foundation of China (92478205, 32371254, 32171190)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
glycans, cryo-electron microscopy, glycan structure, natural water samples
MeSH terms
Models, Molecular, Polysaccharides, Cryoelectron Microscopy

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