Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Effects of Glycans and Hinge on Dynamics in the IgG1 Fc

Published

Author(s)

Christina Bergonzo, J. Todd Hoopes, Zvi Kelman, David Travis Gallagher

Abstract

The crystallizable fragment (Fc) domain of immunoglobulin subclass IgG1 antibodies is engineered for a wide variety of pharmaceutical applications. Two important structural variables in Fc constructs are the hinge region connecting the Fc to the antigen binding fragments (Fab) and the glycans present in various glycoforms. These components affect receptor binding interactions that mediate immune activation. To design new antibody drugs, a robust in silico method for linking stability to structural changes is necessary. In this work, all-atom simulations were used to compare the dynamic behavior of the four structural variants arising from presence or absence of the hinge and glycans. We expressed the simplest of these constructs, the 'minimal Fc' with no hinge and no glycans, in Escherichia coli and report its crystal structure. The 'maximal Fc' that includes full hinge and G0F/G1F glycans is based on a previously reported structure, Protein Data Bank (PDB) ID: 5VGP. These, along with two intermediate structures (with only the glycans or with only the hinge) were used to independently measure the stability effects of the two structural variables using umbrella sampling simulations. Principal component analysis (PCA) was used to determine free energy effects along the Fc's dominant mode of motion. This work provides a comprehensive picture of the effects of hinge and glycans on Fc dynamics and stability.
Citation
Journal of Biomolecular Structure and Dynamics

Keywords

molecular dynamics, crystallography, monoclonal antibody, glycosylation, free energy of interaction, protein structure

Citation

Bergonzo, C. , Hoopes, J. , Kelman, Z. and Gallagher, D. (2023), Effects of Glycans and Hinge on Dynamics in the IgG1 Fc, Journal of Biomolecular Structure and Dynamics, [online], https://doi.org/10.1080/07391102.2023.2270749, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=936516 (Accessed May 18, 2024)

Issues

If you have any questions about this publication or are having problems accessing it, please contact reflib@nist.gov.

Created October 28, 2023, Updated October 30, 2023