Format

Send to

Choose Destination
Angew Chem Int Ed Engl. 2018 Dec 21;57(52):17194-17199. doi: 10.1002/anie.201812018. Epub 2018 Nov 27.

A Mass-Spectrometry-Based Modelling Workflow for Accurate Prediction of IgG Antibody Conformations in the Gas Phase.

Author information

1
Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.
2
Waters Corp., Stamford Road, Wilmslow, SK9 4AX, UK.
3
Randall Centre for Cell and Molecular Biophysics, King's College London, UK.
4
Department of Chemistry, University of Oxford, UK.

Abstract

Immunoglobulins are biomolecules involved in defence against foreign substances. Flexibility is key to their functional properties in relation to antigen binding and receptor interactions. We have developed an integrative strategy combining ion mobility mass spectrometry (IM-MS) with molecular modelling to study the conformational dynamics of human IgG antibodies. Predictive models of all four human IgG subclasses were assembled and their dynamics sampled in the transition from extended to collapsed state during IM-MS. Our data imply that this collapse of IgG antibodies is related to their intrinsic structural features, including Fab arm flexibility, collapse towards the Fc region, and the length of their hinge regions. The workflow presented here provides an accurate structural representation in good agreement with the observed collision cross section for these flexible IgG molecules. These results have implications for studying other nonglobular flexible proteins.

KEYWORDS:

conformation analysis; immunoglobulin; ion mobility; mass spectrometry; molecular dynamics

PMID:
30408305
PMCID:
PMC6392142
DOI:
10.1002/anie.201812018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center