Recent advances in mass spectrometric analysis of protein deamidation

Mass Spectrom Rev. 2017 Nov;36(6):677-692. doi: 10.1002/mas.21491. Epub 2016 Jan 13.

Abstract

Protein deamidation has been proposed to represent a "molecular clock" that progressively disrupts protein structure and function in human degenerative diseases and natural aging. Importantly, this spontaneous process can also modify therapeutic proteins by altering their purity, stability, bioactivity, and antigenicity during drug synthesis and storage. Deamidation occurs non-enzymatically in vivo, but can also take place spontaneously in vitro, hence artificial deamidation during proteomic sample preparation can hamper efforts to identify and quantify endogenous deamidation of complex proteomes. To overcome this, mass spectrometry (MS) can be used to conduct rigorous site-specific characterization of protein deamidation due to the high sensitivity, speed, and specificity offered by this technique. This article reviews recent progress in MS analysis of protein deamidation and discusses the strengths and limitations of common "top-down" and "bottom-up" approaches. Recent advances in sample preparation methods, chromatographic separation, MS technology, and data processing have for the first time enabled the accurate and reliable characterization of protein modifications in complex biological samples, yielding important new data on how deamidation occurs across the entire proteome of human cells and tissues. These technological advances will lead to a better understanding of how deamidation contributes to the pathology of biological aging and major degenerative diseases. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:677-692, 2017.

Keywords: ECD; ERLIC; PIMT; deamidation; isoAsp; mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism*
  • Aging / physiology
  • Aspartic Acid / analysis
  • Aspartic Acid / chemistry
  • Databases, Protein
  • Humans
  • Mass Spectrometry / methods*
  • Neurodegenerative Diseases / metabolism
  • Peptides / analysis
  • Peptides / chemistry
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / chemistry
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase / metabolism
  • Protein Processing, Post-Translational
  • Proteins / analysis*
  • Proteins / chemistry*
  • Proteins / metabolism
  • Proteomics / methods*
  • Reproducibility of Results

Substances

  • Peptides
  • Proteins
  • Aspartic Acid
  • Protein D-Aspartate-L-Isoaspartate Methyltransferase