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Updated: Dec 22, 2025

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Exploring the structure and dynamics of macromolecular complexes by native mass spectrometry
Elisabetta Boeri Erba1, Luca Signor1, Carlo Petosa1
1Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), 38000 Grenoble, France.
Native mass spectrometry (MS) analyzes biomolecular interactions and structures without denaturation. This technique, including native top-down MS, is vital for integrative structural biology and understanding complex macromolecular assemblies.
Area of Science:
- Biochemistry
- Structural Biology
- Analytical Chemistry
Background:
- Mass spectrometry (MS) offers high accuracy, sensitivity, and speed for biomolecule mass determination.
- Native MS, performed under non-denaturing conditions, has been developed over 25 years to study non-covalently associated biomolecules.
Purpose of the Study:
- To illustrate native MS applications for protein-ligand interactions and biomolecular assembly structures.
- To review the use of partial holo-complex dissociation for subunit stoichiometry and topology determination.
- To describe native top-down MS for preserving non-covalent interactions during selective covalent bond fragmentation.
Main Methods:
- Native MS analysis of soluble and membrane protein complexes.
- Partial dissociation of holo-complexes to analyze subunit composition and topology.
- Native top-down MS utilizing Fourier Transform MS (FT MS) for preserving non-covalent interactions.
Main Results:
- Native MS effectively investigates protein-ligand interactions and structures of diverse biomolecular assemblies.
- Partial dissociation in native MS reveals subunit stoichiometry and topology within complexes.
- Native top-down MS enables fragmentation while maintaining non-covalent interactions.
Conclusions:
- Native MS is a powerful tool for studying protein-ligand interactions and complex biomolecular structures.
- The technique aids in determining subunit stoichiometry and topology of macromolecular assemblies.
- Native MS is increasingly crucial for integrative structural biology, elucidating complex macromolecular architectures.
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