Surface-Induced Dissociation of Anionic vs Cationic Native-Like Protein Complexes

J Am Chem Soc. 2021 May 26;143(20):7698-7706. doi: 10.1021/jacs.1c00855. Epub 2021 May 13.

Abstract

Characterizing protein-protein interactions, stoichiometries, and subunit connectivity is key to understanding how subunits assemble into biologically relevant, multisubunit protein complexes. Native mass spectrometry (nMS) has emerged as a powerful tool to study protein complexes due to its low sample consumption and tolerance for heterogeneity. In nMS, positive mode ionization is routinely used and charge reduction, through the addition of solution additives, is often used, as the resulting lower charge states are often considered more native-like. When fragmented by surface-induced dissociation (SID), charge reduced complexes often give increased structural information over their "normal-charged" counterparts. A disadvantage of solution phase charge reduction is that increased adduction, and hence peak broadening, is often observed. Previous studies have shown that protein complexes ionized using negative mode generally form lower charge states relative to positive mode. Here we demonstrate that the lower charged protein complex anions activated by surface collisions fragment in a manner consistent with their solved structures, hence providing substructural information. Negative mode ionization in ammonium acetate offers the advantage of charge reduction without the peak broadening associated with solution phase charge reduction additives and provides direct structural information when coupled with SID. SID of 20S human proteasome (a 28-mer comprised of four stacked heptamer rings in an αββα formation), for example, provides information on both substructure (e.g., splitting into a 7α ring and the corresponding ββα 21-mer, and into α dimers and trimers to provide connectivity around the 7 α ring) and proteoform information on monomers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anions / chemistry
  • Cations / chemistry
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Proteins / chemistry*
  • Surface Properties

Substances

  • Anions
  • Cations
  • Proteins