Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 50, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2116325118
Keywords
methyl-TROSY; human high-temperature requirement A2 protein; proteasome; ClpP1P2; p97/VCP
Categories
Funding
- Japan Society for the Promotion of Science Overseas Research Fellowship
- Uehara Memorial Foundation
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
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Developments in solution NMR spectroscopy have significantly impacted the ability to address biological questions, especially in studying molecular machines critical for cellular homeostasis. NMR plays a key role in elucidating the structural dynamics of important molecules, highlighting intersubunit allosteric communication in homo-oligomers. Through focused experimental studies on individual subunits and the preparation of asymmetric molecules, intersubunit allostery can be directly observed in high-molecular-weight protein systems, showcasing the unique contributions of solution NMR spectroscopy in studying complex biomolecules and emphasizing the synergy between NMR and other atomic resolution biophysical methods.
Developments in solution NMR spectroscopy have significantly impacted the biological questions that can now be addressed by this methodology. By means of illustration, we present here a perspective focusing on studies of a number of molecular machines that are critical for cellular homeostasis. The role of NMR in elucidating the structural dynamics of these important molecules is emphasized, focusing specifically on intersubunit allosteric communication in homo-oligomers. In many biophysical studies of oligomers, allostery is inferred by showing that models specifically including intersubunit communication best fit the data of interest. Ideally, however, experimental studies focusing on one subunit of a multisubunit system would be performed as an important complement to the more traditional bulk measurements in which signals from all components are measured simultaneously. Using an approach whereby asymmetric molecules are prepared in concert with NMR experiments focusing on the structural dynamics of individual protomers, we present examples of how intersubunit allostery can be directly observed in high-molecular-weight protein systems. These examples highlight some of the unique roles of solution NMR spectroscopy in studies of complex biomolecules and emphasize the important synergy between NMR and other atomic resolution biophysical methods.
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