Uncovering the Conformational Distribution of a Small Protein with Nanoparticle-Aided Cryo-Electron Microscopy Sampling

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Here, we introduce the nanoparticle-aided cryo-electron microscopy sampling (NACS) method to access the conformational distribution of a protein molecule. Two nanogold particles are labeled at two target sites, and the interparticle distance is measured as a structural parameter via cryo-electron microscopy (cryo-EM). The key aspect of NACS is that the projected distance information instead of the global conformational information is extracted from each protein molecule. This is possible because the contrast provided by the nanogold particles is strong enough to provide the projected distance, while the protein itself is invisible due to its low contrast. We successfully demonstrate that various protein conformations, even for small or disordered proteins, which generally cannot be accessed via cryo-EM, can be captured. The demonstrated method with the potential to directly observe the conformational distribution of such systems may open up new possibilities in studying their dynamics at a single-molecule level.
Publisher
AMER CHEMICAL SOC
Issue Date
2021-07
Language
English
Article Type
Article
Citation

JOURNAL OF PHYSICAL CHEMISTRY LETTERS, v.12, no.28, pp.6565 - 6573

ISSN
1948-7185
DOI
10.1021/acs.jpclett.1c01277
URI
http://hdl.handle.net/10203/287081
Appears in Collection
MSE-Journal Papers(저널논문)PH-Journal Papers(저널논문)CH-Journal Papers(저널논문)
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