Mass Spectrometry-Based Approaches for Protein Higher Order Structure Analysis
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Eli Lilly and Company
Yining Huang is a research scientist at Eli Lilly and company. At Lilly, he supports drug development for pre-clinical…
Bristol Myers Squibb
Xiaoran Roger Liu is a scientist at Bristol Myers Squibb. At BMS, he is responsible for supporting mass spectrometry…
Proteins adopt different higher order structures (HOS) to enable their unique biological functions. Understanding the complexities of protein higher order structures and dynamics requires integrated approaches, therefore, mass spectrometry (MS) is now positioned to play a key role. Although MS-based approaches are unable to deliver atomic coordinates of target protein, they have the advantages of mid-to-high structural or spatial resolution, specificity, low sample amount requirement, high throughput, and proteomics capabilities.
To date, many MS-based approaches have contributed significantly to the protein HOS analysis, such as: tandem MS (MS/MS)-based de novo sequencing for primary sequence elucidation, native MS that maintains noncovalent interactions in the gas phase for intact proteins and protein complexes, cross-linking MS that delivers primarily stoichiometry and topological information of protein complexes, ion-mobility MS that reports protein shape in the gas phase, hydrogen deuterium exchange MS for protein structure and dynamics analysis, and labeling-based footprinting that probes changes in solvent accessibilities through differential experiments. All these approaches combined form a “toolbox” which allows MS to be a valuable tool in elucidating protein HOS.
In this method collection, we plan to include topics that cover different MS-based HOS analysis approaches. Our goal is to assemble a collection of methods that relates tools to biological questions that they can address. Readers can thus pick up proper methods to address their questions of interest.