Methyl-Based NMR Spectroscopy Methods for Uncovering Structural Dynamics in Large Proteins and Protein Complexes

Zachary K. Boswell, Michael P. Latham

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations


NMR spectroscopy is particularly adept at site-specifically monitoring dynamic processes in proteins, such as protein folding, domain movements, ligand binding, and side-chain rotations. By coupling the favorable spectroscopic properties of highly dynamic side-chain methyl groups with transverse-relaxation-optimized spectroscopy (TROSY), it is now possible to routinely study such dynamic processes in high-molecular-weight proteins and complexes approaching 1 MDa. In this Perspective, we describe many elegant methyl-based NMR experiments that probe slow (second) to fast (picosecond) dynamics in large systems. To demonstrate the power of these methods, we also provide interesting examples of studies that utilized each methyl-based NMR technique to uncover functionally important dynamics. In many cases, the NMR experiments are paired with site-directed mutagenesis and/or other biochemical assays to put the dynamics and function into context. Our vision of the future of structural biology involves pairing methyl-based NMR spectroscopy with biochemical studies to advance our knowledge of the motions large proteins and macromolecular complexes use to choreograph complex functions. Such studies will be essential in elucidating the critical structural dynamics that underlie function and characterizing alterations in these processes that can lead to human disease.

Original languageEnglish (US)
Pages (from-to)144-155
Number of pages12
Issue number3
StatePublished - Jan 22 2019
Externally publishedYes

Bibliographical note

Funding Information:
Research in the Latham laboratory is supported by grants from the Welch Foundation (D-1876), the Cancer Prevention Research Institute of Texas (RP180553) and the National Institute of General Medical Sciences, NIH (1R35GM128906).

Publisher Copyright:
© 2018 American Chemical Society.


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