Microchip-based structure determination of low-molecular weight proteins using cryo-electron microscopy

Interest in cryo-Electron Microscopy (EM) imaging has skyrocketed in recent years due to its pristine views of macromolecules and materials. As advances in instrumentation and computing algorithms spurred this progress, there is renewed focus to address specimen-related challenges. Here we contribute a microchip-based toolkit to perform complementary structural and biochemical analysis on low-molecular weight proteins. As a model system, we used the SARS-CoV-2 nucleocapsid (N) protein (48 kDa) due to its stability and important role in therapeutic development. Cryo-EM structures of the N protein monomer revealed a flexible N-terminal "top hat"motif and a helical-rich C-terminal domain. To complement our structural findings, we engineered microchip-based immunoprecipitation assays that led to the discovery of the first antibody binding site on the N protein. The data also facilitated molecular modeling of a variety of pandemic and common cold-related coronavirus proteins. Such insights may guide future pandemic-preparedness protocols through immuno-engineering strategies to mitigate viral outbreaks. This journal is



Work Title Microchip-based structure determination of low-molecular weight proteins using cryo-electron microscopy
Open Access
  1. Michael A. Casasanta
  2. G. M. Jonaid
  3. Liam Kaylor
  4. William Y. Luqiu
  5. Maria J. Solares
  6. Mariah L. Schroen
  7. William J. Dearnaley
  8. Jarad Wilson
  9. Madeline J. Dukes
  10. Deborah F. Kelly
License In Copyright (Rights Reserved)
Work Type Article
  1. Nanoscale
Publication Date April 21, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1039/d1nr00388g
Deposited July 15, 2021




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Work History

Version 1

  • Created
  • Added Nanoscale-revision.pdf
  • Added Creator Michael A. Casasanta
  • Added Creator G. M. Jonaid
  • Added Creator Liam Kaylor
  • Added Creator William Y. Luqiu
  • Added Creator Maria J. Solares
  • Added Creator Mariah L. Schroen
  • Added Creator William J. Dearnaley
  • Added Creator Jarad Wilson
  • Added Creator Madeline J. Dukes
  • Added Creator Deborah F. Kelly
  • Published
  • Updated
  • Updated