Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry.

Chemical Science
Mowei ZhouFrederik Lermyte

Abstract

In biology, it can be argued that if the genome contains the script for a cell's life cycle, then the proteome constitutes an ensemble cast of actors that brings these instructions to life. Their interactions with each other, co-factors, ligands, substrates, and so on, are key to understanding nearly any biological process. Mass spectrometry is well established as the method of choice to determine protein primary structure and location of post-translational modifications. In recent years, top-down fragmentation of intact proteins has been increasingly combined with ionisation of noncovalent assemblies under non-denaturing conditions, i.e., native mass spectrometry. Sequence, post-translational modifications, ligand/metal binding, protein folding, and complex stoichiometry can thus all be probed directly. Here, we review recent developments in this new and exciting field of research. While this work is written primarily from a mass spectrometry perspective, it is targeted to all bioanalytical scientists who are interested in applying these methods to their own biochemistry and chemical biology research.

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Citations

May 1, 2021·Viruses·Yogy SimanjuntakPietro Scaturro
May 1, 2021·Current Opinion in Structural Biology·Mark T Agasid, Carol V Robinson
May 14, 2021·Journal of the American Society for Mass Spectrometry·Jake A MelbyYing Ge
Nov 26, 2020·Journal of the American Society for Mass Spectrometry·Frederik LermytePeter B O'Connor
Sep 3, 2021·Chemical Reviews·Amber D Rolland, James S Prell
Oct 30, 2021·Journal of the American Society for Mass Spectrometry·Luis A MaciasJennifer S Brodbelt
Nov 3, 2021·Chemical Reviews·Dalton T SnyderVicki H Wysocki
Dec 1, 2021·Journal of Proteome Research·Brandon T Ruotolo

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Methods Mentioned

BETA
environmental stress
footprinting
X-ray
nuclear magnetic resonance
electron microscopy
electron capture dissociation
infrared spectroscopy
electrophoresis
NMR
protein folding

Software Mentioned

ProSight PTM
Informed
TDMS
UVPD
Masstodon
ExD
Proteomics
UniDec
MASH Suite
ProSight Lite

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