Direct observation of glycans bonded to proteins and lipids at the single-molecule level

Science. 2023 Oct 13;382(6667):219-223. doi: 10.1126/science.adh3856. Epub 2023 Oct 12.

Abstract

Proteins and lipids decorated with glycans are found throughout biological entities, playing roles in biological functions and dysfunctions. Current analytical strategies for these glycan-decorated biomolecules, termed glycoconjugates, rely on ensemble-averaged methods that do not provide a full view of positions and structures of glycans attached at individual sites in a given molecule, especially for glycoproteins. We show single-molecule analysis of glycoconjugates by direct imaging of individual glycoconjugate molecules using low-temperature scanning tunneling microscopy. Intact glycoconjugate ions from electrospray are soft-landed on a surface for their direct single-molecule imaging. The submolecular imaging resolution corroborated by quantum mechanical modeling unveils whole structures and attachment sites of glycans in glycopeptides, glycolipids, N-glycoproteins, and O-glycoproteins densely decorated with glycans.

MeSH terms

  • Glycoconjugates / chemistry
  • Glycolipids / chemistry
  • Glycoproteins* / chemistry
  • Mucin-1 / chemistry
  • Polysaccharides* / chemistry
  • Single Molecule Imaging*

Substances

  • Glycoconjugates
  • Glycolipids
  • Glycoproteins
  • Polysaccharides
  • MUC1 protein, human
  • Mucin-1