Mass spectrometry guided structural biology
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Updated: Mar 13, 2026

Analyzing Large Protein Complexes by Structural Mass Spectrometry
Published on: June 19, 2010
Idlir Liko1, Timothy M Allison1, Jonathan Ts Hopper1
1Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford, OX1 3QZ, United Kingdom.
Abstract:
With the convergence of breakthroughs in structural biology, specifically breaking the resolution barriers in cryo-electron microscopy and with continuing developments in crystallography, novel interfaces with other biophysical methods are emerging. Here we consider how mass spectrometry can inform these techniques by providing unambiguous definition of subunit stoichiometry. Moreover recent developments that increase mass spectral resolution enable molecular details to be ascribed to unassigned density within high-resolution maps of membrane and soluble protein complexes. Importantly we also show how developments in mass spectrometry can define optimal solution conditions to guide downstream structure determination, particularly of challenging biomolecules that refuse to crystallise.
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