Document Type
Article
Publication Date
4-17-2020
Abstract
Structural biology is entering an exciting time where many new high-resolution structures of large complexes and membrane proteins are determined regularly. These advances have been driven by over fifteen years of technology advancements, first in macromolecular crystallography, and recently in Cryo-electron microscopy. These structures are allowing detailed questions about functional mechanisms of the structures, and the biology enabled by these structures, to be addressed for the first time. At the same time, mass spectrometry technologies for protein structure analysis, “footprinting” studies, have improved their sensitivity and resolution dramatically and can provide detailed sub-peptide and residue level information for validating structures and interactions or understanding the dynamics of structures in the context of ligand binding or assembly. In this perspective, we review the use of protein footprinting to extend our understanding of macromolecular systems, particularly for systems challenging for analysis by other techniques, such as intrinsically disordered proteins, amyloidogenic proteins, and other proteins/complexes so far recalcitrant to existing methods. We also illustrate how the availability of high-resolution structural information can be a foundation for a suite of hybrid approaches to divine structure-function relationships beyond what individual techniques can deliver.
Keywords
footprinting, hybrid methods, mass spectrometry, proteins, structural biology
Publication Title
Journal of Molecular Biology
Volume
432
Issue
9
First Page
2973
Last Page
2984
Rights
©2020 The Authors. Published by Elsevier Ltd.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Mark R. Chance, Erik R. Farquhar, Sichun Yang, David T. Lodowski, Janna Kiselar. Protein Footprinting: Auxiliary Engine to Power the Structural Biology Revolution. Journal of Molecular Biology, Volume 432, Issue 9, 2020, Pages 2973-2984, https://doi.org/10.1016/j.jmb.2020.02.011.