Identification of tagged glycans with a protein nanopore

Minmin Li, Yuting Xiong, Yuchen Cao, Chen Zhang, Yuting Li, Hanwen Ning, Fan Liu, Han Zhou, Xiaonong Li, Xianlong Ye, Yue Pang, Jiaming Zhang, Xinmiao Liang () and Guangyan Qing ()
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Minmin Li: Chinese Academy of Sciences
Yuting Xiong: Chinese Academy of Sciences
Yuchen Cao: Chinese Academy of Sciences
Chen Zhang: Ganjiang Chinese Medicine Innovation Center
Yuting Li: Ganjiang Chinese Medicine Innovation Center
Hanwen Ning: Zhongnan University of Economics and Law
Fan Liu: Chinese Academy of Sciences
Han Zhou: Chinese Academy of Sciences
Xiaonong Li: Ganjiang Chinese Medicine Innovation Center
Xianlong Ye: Ganjiang Chinese Medicine Innovation Center
Yue Pang: Liaoning Normal University
Jiaming Zhang: Zhongnan University of Economics and Law
Xinmiao Liang: Chinese Academy of Sciences
Guangyan Qing: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Structural complexity of glycans derived from the diversities in composition, linage, configuration, and branching considerably complicates structural analysis. Nanopore-based single-molecule sensing offers the potential to elucidate glycan structure and even sequence glycan. However, the small molecular size and low charge density of glycans have restricted direct nanopore detection of glycan. Here we show that glycan sensing can be achieved using a wild-type aerolysin nanopore by introducing a facile glycan derivatization strategy. The glycan molecule can induce impressive current blockages when moving through the nanopore after being connected with an aromatic group-containing tag (plus a carrier group for the neutral glycan). The obtained nanopore data permit the identification of glycan regio- and stereoisomers, glycans with variable monosaccharide numbers, and distinct branched glycans, either independently or with the use of machine learning methods. The presented nanopore sensing strategy for glycans paves the way towards nanopore glycan profiling and potentially sequencing.

Date: 2023
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DOI: 10.1038/s41467-023-37348-5

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