Mass spectrometry analysis of the structural proteome

Area of Science:

• Biochemistry
• Proteomics
• Structural Biology

Background:

• Mass spectrometry (MS)-based proteomics traditionally focuses on protein identification.
• There is a growing need to understand protein structure and dynamics at a large scale.

Purpose of the Study:

• To provide an overview of MS-based methods for assessing proteome-wide structural and biophysical properties.
• To highlight the potential of these methods in advancing structural systems biology.

Main Methods:

• Cross-linking-MS
• Limited proteolysis-MS
• Co-fractionation-MS
• Hydroxyl radical footprinting-MS
• Thermal proteome profiling
• MS approaches for monitoring molecular interactions

Main Results:

• MS can quantitatively probe complex protein mixtures to study structural and biophysical properties.
• These methods provide readouts for proteome-wide structural alterations, folding, stability, aggregation, and molecular interactions.
• Analysis can be performed under native-like conditions, including cell lysates and intact cells.

Conclusions:

• Proteome-scale structural and biophysical analysis using MS is a rapidly advancing field.
• These methods are crucial for understanding cellular function and disease mechanisms.
• The integration of these MS techniques will drive the field of structural systems biology.