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Methods Collections

Mass Spectrometry-Based Approaches for Protein Higher Order Structure Analysis

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Methods Collections
Mass Spectrometry-Based Approaches for Protein Higher Order Structure Analysis

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…

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…

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.


Automation of In-Cell Fast Photochemical Oxidation of Proteins (IC-FPOP) in a Static Platform

Danté Johnson*1, Benjamin Punshon-Smith2, Anne Gershenson3, Lisa Jones*1
1University of Maryland, 2University of Maryland Baltimore County, 3University of Massachusetts Amherst

In vivo cross-linking mass spectrometry for protein and complex structural analysis

James Bruce*1, Juan Chavez2, Andrew Keller2, Helisa Wippel3
1Univrsity of Washington, 2University of Washington, 3Unversity of Washington

Covalent Labeling with Diethylpyrocarbonate for Studying Protein Structure by Mass Spectrometry

Richard Vachet*1, Blaise Arden1, Patanachai Limpikirati2, Zachary Kirsch1
1Department of Chemistry, University of Massachusetts Amherst, 2Department of Food and Pharmaceutical Chemistry, Chulalongkorn University

Laser-Free Flash Photo-oxidation of Proteins for Hydroxyl Radical Protein Footprinting

Scot Weinberger*1
1GenNext Technologies Inc.

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