4.7 Article

Protein Footprinting: Auxiliary Engine to Power the Structural Biology Revolution

期刊

JOURNAL OF MOLECULAR BIOLOGY
卷 432, 期 9, 页码 2973-2984

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2020.02.011

关键词

proteins; mass spectrometry; structural biology; footprinting; hybrid methods

资金

  1. National Institute of General Medicine Sciences (NIH) [R01-GM114056]
  2. Mt. Sinai Healthcare Foundation
  3. National Science Foundation, Division of Biological Infrastructure [1228549]
  4. DOE Office of Science [DE-SC0012704]
  5. [P30-EB-009998]
  6. Div Of Biological Infrastructure
  7. Direct For Biological Sciences [1228549] Funding Source: National Science Foundation

向作者/读者索取更多资源

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. (C) 2020 The Authors. Published by Elsevier Ltd.

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