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Updated: Jul 18, 2026

Mass-Sensitive Particle Tracking to Characterize Membrane-Associated Macromolecule Dynamics
Published on: February 18, 2022
Top-down mass spectrometry of integral membrane proteins
Julian Whitelegge1, Frederic Halgand, Puneet Souda
1University of California, Pasarow Mass Spectrometry Laboratory, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, Los Angeles, CA 90024, USA. jpw@chem.ucla.edu
Abstract:
Top-down mass spectrometry focuses on intact proteins, thereby avoiding loss of information accompanying 'shotgun' protocols that reduce the proteome to a collection of peptides. A suite of liquid-chromatography technologies has been developed for purification of intact integral membrane proteins in aqueous/organic solvent mixtures compatible with biological 'soft-ionization' mass spectrometry, preserving covalent structure into the gas phase. Multiply charged protein ions are fragmented in the gas phase, using either collision-activated or electron-capture dissociation, thus yielding complex spectra of sequence-dependent product ions that collectively define the original native covalent state of an intact protein. Top down offers a more detail-orientated approach to post-transcriptional and post-translational diversity allowing an enhanced insight beyond genomic translation, which has now extended into the bilayer proteome.
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