Document Type
Article
Publication Date
11-7-2016
Abstract
Isoforms of the Fcγ receptor III (FcγRIII or CD16) are cell surface receptors for the Fc portion of IgG and important regulators of humoral immune responses. Different ligand binding kinetics of FcγRIII isoforms are obtained in three dimensions by surface plasmon resonance and in two dimensions by a micropipette adhesion frequency assay. We show that the anchor structure of CD16 isoforms isolated from the cell membrane affects their binding affinities in a ligand-specific manner. Changing the receptor anchor structure from full to partial to none decreases the ligand binding affinity for human IgG1 (hIgG1) but increases it for murine IgG2a (mIgG2a). Removing N-glycosylation from the CD16 protein core by tunicamycin also increases the ligand binding affinity. Molecular dynamics simulations indicate that deglycosylation at Asn-163 of CD16 removes the steric hindrance for the CD16-hIgG1 Fc binding and thus increases the binding affinity. These results highlight an unexpected sensitivity of ligand binding to the receptor anchor structure and glycosylation and suggest their respective roles in controlling allosterically the conformation of the ligand binding pocket of CD16.
Publication Title
Molecular Biology of the Cell
Volume
27
Issue
22
First Page
3449
Last Page
3458
Recommended Citation
Jiang, Ning; Chen, Wei; Jothikumar, Prithiviraj; Patel, Jaina M.; Shashidharamurthy, Rangaiah; Selvaraj, Periasamy; and Zhu, Cheng, "Effects of Anchor Structure and Glycosylation of Fcγ Receptor III on Ligand Binding Affinity" (2016). PCOM Scholarly Works. 1756.
https://digitalcommons.pcom.edu/scholarly_papers/1756
Comments
This article was published in Molecular Biology of the Cell, Volume 27, Issue 22, Pages 3449-3458.
The published version is available at http://dx.doi.org/10.1091/mbc.E16-06-0470.
Copyright © 2016.