Dynamics of Intact Immunoglobulin G Explored by Drift-Tube Ion-Mobility Mass Spectrometry and Molecular Modeling

• Published in: Angewandte Chemie International Edition 2014-07, Vol.53 (30), p.7765-7769
• Main Authors: Pacholarz, Kamila J., Porrini, Massimiliano, Garlish, Rachel A., Burnley, Rebecca J., Taylor, Richard J., Henry, Alistair J., Barran, Perdita E.
• Format: Article
• Language: English
• Subjects: conformation analysis; Immunoglobulin G - chemistry; immunoglobulin G; mass spectrometry; Mass Spectrometry - methods; Models, Molecular; molecular dynamics; Protein Conformation; protein structures
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201402863

Collision cross‐sections (CCS) of immunoglobulins G1 and G4 have been determined using linear drift‐tube ion‐mobility mass spectrometry. Intact antibodies and Fc‐hinge fragments present with a larger range of CCS than proteins of comparable size. This is rationalized with MD simulations, which indicate significant in vacuo dynamics between linked folded domains. The IgG4 subclass presents over a wider CCS range than the IgG1 subclass. Dancing antibodies: Collision cross‐sections of immunoglobulins G1 and G4 have been determined using linear drift‐tube ion‐mobility mass spectrometry. Intact antibodies and Fc hinge fragments possess far higher intrinsic flexibility than proteins of comparable size. This is rationalized with MD simulations, which reveal dynamics between linked folded domains. The IgG1 subclass is less dynamic than the IgG4 subclass in the absence of solvent.