Native Ambient Mass Spectrometry Imaging of Ligand-Bound and Metal-Bound Proteins in Rat Brain

Research output: Contribution to journalArticlepeer-review

49 Downloads (Pure)


Label-free spatial mapping of the noncovalent interactions of proteins in their tissue environment has the potential to revolutionize life sciences research by providing opportunities for the interrogation of disease progression, drug interactions, and structural and molecular biology more broadly. Here, we demonstrate mass spectrometry imaging of endogenous intact noncovalent protein-ligand complexes in rat brain. The spatial distributions of a range of ligand-bound and metal-bound proteins were mapped in thin tissue sections by use of nanospray-desorption electrospray ionization. Proteins were identified directly from the tissue by top-down mass spectrometry. Three GDP-binding proteins (ADP ribosylation factor ARF3, ARF1, and GTPase Ran) were detected, identified, and imaged in their ligand-bound form. The nature of the ligand was confirmed by multiple rounds of tandem mass spectrometry. In addition, the metal-binding proteins parvalbumin-α and carbonic anhydrase 2 were detected, identified, and imaged in their native form, i.e., parvalbumin-α + 2Ca2+ and carbonic anhydrase + Zn2+. GTPase Ran was detected with both GDP and Mg2+ bound. Several natively monomeric proteins displaying distinct spatial distributions were also identified by top-down mass spectrometry. Protein mass spectrometry imaging was achieved at a spatial resolution of 200 μm.

Original languageEnglish
Pages (from-to)2120-2128
Number of pages9
JournalJournal of the American Chemical Society
Issue number5
Early online date25 Jan 2022
Publication statusPublished - 9 Feb 2022

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


Dive into the research topics of 'Native Ambient Mass Spectrometry Imaging of Ligand-Bound and Metal-Bound Proteins in Rat Brain'. Together they form a unique fingerprint.

Cite this