Chemical Crosslinking-Mass Spectrometry (CXL-MS) for Proteomics, Antibody-Drug Conjugates (ADCs) and Cryo-Electron Microscopy (cryo-EM)

IUBMB Life. 2018 Oct;70(10):947-960. doi: 10.1002/iub.1916. Epub 2018 Sep 3.

Abstract

Chemical crosslinking-mass spectrometry (CXL-MS) has emerged as a powerful tool in structural biology to elucidate protein-protein interactions. This review throws light on the advent of these technologies incorporating chemical crosslinking in proteomics, structural biology and extended to studies and applications of antibody-drug conjugates (ADCs). Monoclonal ASCs are known to target their specific receptors, where the drug could be released for vastly improved therapeutic effect. Cryo-electron microscopy (cryo-EM) is being referred to as the "revolution of the century" as it can help attain almost atomic resolution, while preserving the biological samples at near-native state and has been recognized by the Nobel award 2017. CXL-MS and appropriate bioinformatics tools in combination with cryo-EM reveal better 3D information about dynamic interactions in proteins, interactive domains and motifs, among others in ADCs and in viruses like Zika virus, Rota virus, Dengue virus and also spliceosomes at resolutions, especially below 3 Å. © 2018 IUBMB Life, 70(10):947-960, 2018.

Keywords: antibody-drug conjugates; chemical crosslinkers; cryo-EM; proteomics.

Publication types

  • Review

MeSH terms

  • Cross-Linking Reagents / chemistry*
  • Cryoelectron Microscopy / methods*
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / isolation & purification
  • Mass Spectrometry / methods
  • Proteins / chemistry
  • Proteins / isolation & purification*
  • Proteomics / trends*

Substances

  • Cross-Linking Reagents
  • Immunoconjugates
  • Proteins