Native Mass Spectrometry: What is in the Name?

Area of Science:

• Biomolecular mass spectrometry
• Structural biology
• Proteomics

Background:

• Electrospray ionization mass spectrometry (ESI-MS) is a cornerstone of modern biomolecular analysis.
• Advances allow extraction of more than molecular weight, including noncovalent complexes.
• Native MS emerged to study protein, DNA, and RNA assemblies in their native quaternary state.

Purpose of the Study:

• To redefine and trace the origins of the term "native MS."
• To clarify the scope and limitations of native MS.
• To showcase native MS applications in solving biological questions.

Main Methods:

• Electrospray ionization mass spectrometry (ESI-MS)
• Analysis of noncovalent protein-protein and protein-ligand complexes
• Preservation of native quaternary structure in the gas phase

Main Results:

• Native MS has matured over two decades, with widespread laboratory adoption.
• The technique successfully analyzes diverse biomolecular assemblies, including protein, DNA, and RNA complexes.
• Numerous examples demonstrate native MS's capability in addressing complex biological inquiries.

Conclusions:

• Native MS is a powerful tool for structural biology and understanding biological mechanisms.
• The definition and scope of native MS have been clarified.
• The technology offers broad potential for elucidating structure-function relationships.