Journal
CHEMICAL REVIEWS
Volume 122, Issue 8, Pages 7952-7986Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrev.1c00356
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Funding
- Wellcome Trust [221521/Z/20/Z, 104913/Z/14/Z.]
- Wellcome Trust [104913/Z/14/Z, 221521/Z/20/Z] Funding Source: Wellcome Trust
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Mass spectrometry is increasingly used in the study of protein structure and dynamics. Structural MS methods provide unique structural information, and computational strategies are essential for integrating diverse data. Combining structural MS with other techniques is often necessary to capture the full structural details of a system. The integration of structural MS data has been fruitful in solving the structures of complex protein assemblies.
Mass spectrometry (MS) is increasingly being used to probe the structure and dynamics of proteins and the complexes they form with other macromolecules. There are now several specialized MS methods, each with unique sample preparation, data acquisition, and data processing protocols. Collectively, these methods are referred to as structural MS and include cross-linking, hydrogen-deuterium exchange, hydroxyl radical footprinting, native, ion mobility, and top-down MS. Each of these provides a unique type of structural information, ranging from composition and stoichiometry through to residue level proximity and solvent accessibility. Structural MS has proved particularly beneficial in studying protein classes for which analysis by classic structural biology techniques proves challenging such as glycosylated or intrinsically disordered proteins. To capture the structural details for a particular system, especially larger multiprotein complexes, more than one structural MS method with other structural and biophysical techniques is often required. Key to integrating these diverse data are computational strategies and software solutions to facilitate this process. We provide a background to the structural MS methods and briefly summarize other structural methods and how these are combined with MS. We then describe current state of the art approaches for the integration of structural MS data for structural biology. We quantify how often these methods are used together and provide examples where such combinations have been fruitful. To illustrate the power of integrative approaches, we discuss progress in solving the structures of the proteasome and the nuclear pore complex. We also discuss how information from structural MS, particularly pertaining to protein dynamics, is not currently utilized in integrative workflows and how such information can provide a more accurate picture of the systems studied. We conclude by discussing new developments in the MS and computational fields that will further enable in-cell structural studies.
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