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Updated: Dec 29, 2025

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Native Mass Spectrometry: What is in the Name?
Aneika C Leney1,2, Albert J R Heck1,2
1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Padualaan 8 , 3584CH , Utrecht , The Netherlands.
Native MS, a technique using electrospray ionization mass spectrometry, analyzes large biomolecular assemblies like protein complexes. This method retains their native structure for studying biological functions.
Area of Science:
- Biomolecular mass spectrometry
- Structural biology
- Proteomics
Background:
- Electrospray ionization mass spectrometry (ESI-MS) has advanced beyond molecular weight determination.
- Noncovalent protein-protein and protein-ligand complexes are now analyzable by MS.
- Maintaining native quaternary structure in the gas phase is crucial for analyzing assemblies.
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 the application of native MS in structural biology and understanding structure-function relationships.
Main Methods:
- Utilizes electrospray ionization mass spectrometry (ESI-MS).
- Focuses on preserving the native quaternary state of biomolecular assemblies in the gas phase.
- Employs advanced sample preparation and mass analyzers.
Main Results:
- Native MS has matured over two decades, becoming a key technique.
- It is widely used to study protein, DNA, and RNA-protein assemblies.
- Numerous studies demonstrate its success in addressing complex biological questions.
Conclusions:
- Native MS is a powerful tool for structural biology, enabling the study of intact biomolecular assemblies.
- The technique provides insights into structure-function relationships of complex biological systems.
- Clarifying the definition and scope of native MS is essential for its continued advancement and application.
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