Mass Spectrometry-Based Approaches for Protein Higher Order Structure Analysis

TOPICAL COLLECTIONS

Guest Editors

Yining Huang

Eli Lilly and Company

Yining Huang is a research scientist at Eli Lilly and company. At Lilly, he supports drug development for pre-clinical and clinical stage assets, including monoclonal antibodies and therapeutic proteins using mass spectrometry-based protein characterization techniques. Dr. Huang is also leading collaborations between Lilly and academic institutions on the topic of protein higher-order structure analysis by MS. Dr. Huang received his BS in Chemistry from Peking University and earned his PhD in Chemistry from Washington University in St. Louis. In his graduate research with Dr. Michael L. Gross, he focused on implementing MS-based methods, including: hydrogen-deuterium exchange, fast photochemical oxidation of proteins, native MS, as well as ion mobility for studying protein-protein interactions in malaria and viral infectious diseases. Dr. Huang was a recipient of the McDonell Scholarship at Washington University. In his academic and research career, he authored and co-authored multiple publications in protein structural studies, which are crucial for vaccine and therapy development.

Xiaoran Roger Liu

Bristol Myers Squibb

Xiaoran Roger Liu is a scientist at Bristol Myers Squibb. At BMS, he is responsible for supporting mass spectrometry capabilities in support of bioprocess development and analytical strategies for protein characterization, release and stability, and impurity profiling. Dr. Liu earned his PhD with Dr. Michael L. Gross from Washington University in St. Louis (Missouri, U.S.), focusing on the characterization of protein higher order structures through developing and applying novel mass spectrometry-based approaches, most notably: fast photochemical oxidation of proteins, hydrogen deuterium exchange, footprinting by targeted reagents, and native spray. Prior to his PhD study, he received his BE in Applied Chemistry from East China University of Science and Technology (Shanghai, China) and MS in Polymer Science from the College of Polymer Science and Polymer Engineering, The University of Akron (Ohio, U.S.). He has authored and coauthored over 12 publications, delivered oral and poster presentations for various conferences, and served as a peer reviewer for many journals. His scientific contributions and community engagements have been recognized with numerous awards, most recently the Lake Louise Marg Northcott Award by Canadian Society for Mass Spectrometry.

Collection Overview

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.