Structural Characterization of Native Proteins and Protein Complexes by Electron Ionization Dissociation-Mass Spectrometry

Li, Huilin; Sheng, Yuewei; McGee, William; Cammarata, Michael; Holden, Dustin; Loo, Joseph A.

doi:10.1021/acs.analchem.6b02377

Title: Structural Characterization of Native Proteins and Protein Complexes by Electron Ionization Dissociation-Mass Spectrometry

Journal Article · Tue Feb 07 00:00:00 EST 2017 · Analytical Chemistry

DOI:https://doi.org/10.1021/acs.analchem.6b02377· OSTI ID:1463126

Li, Huilin ^[1]; Sheng, Yuewei ^[1]; McGee, William ^[2]; Cammarata, Michael ^[2]; Holden, Dustin ^[2];

^[1]

Univ. of California, Los Angeles, CA (United States)
Univ. of Texas, Austin, TX (United States)

Mass spectrometry (MS) has played an increasingly important role in the identification and structural and functional characterization of proteins. In particular, the use of tandem mass spectrometry has afforded one of the most versatile methods to acquire structural information for proteins and protein complexes. The unique nature of electron capture dissociation (ECD) for cleaving protein backbone bonds while preserving non-covalent interactions has made it especially suitable for the study of native protein structures. However, the intra- and inter-molecular interactions stabilized by hydrogen bonds and salt bridges can hinder the separation of fragments even with pre-activation, which has become particularly problematic for the study of large macromolecular proteins and protein complexes. Here, we describe the capabilities of another activation method, 30 eV electron ionization dissociation (EID), for the top-down MS characterization of native protein-ligand and protein-protein complexes. Rich structural information that cannot be delivered by ECD can be generated by EID. EID allowed for the comparison of the gas-phase and the solution-phase structural stability and unfolding process of human carbonic anhydrase I (HCA-I). In addition, the EID fragmentation patterns reflect the structural similarities and differences among apo-, Zn-, and Cu,Zn-superoxide dismutase (SOD1) dimers. In particular, the structural changes due to Cu-binding and a point mutation (G41D) were revealed by EID-MS. The performance of EID was also compared to that of 193 nm ultraviolet photodissociation (UVPD), which allowed us to explore their qualitative similarities and differences as potential valuable tools for the MS study of native proteins and protein complexes.

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Research Organization:: Univ. of California, Los Angeles, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: FC03-02ER63421

OSTI ID:: 1463126

Journal Information:: Analytical Chemistry, Vol. 89, Issue 5; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 52 works

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