Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/13073
Title: Multiple regions of human Fc gamma RII (CD32) contribute to the binding of IgG.
Authors: Hulett, M D;Witort, E;Brinkworth, R I;McKenzie, Ian F C;Hogarth, P Mark
Affiliation: Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Issue Date: 8-Sep-1995
Citation: The Journal of Biological Chemistry; 270(36): 21188-94
Abstract: The low affinity receptor for IgG, Fc gamma RII (CD32), has a wide distribution on hematopoietic cells where it is responsible for a diverse range of cellular responses crucial for immune regulation and resistance to infection. Fc gamma RII is a member of the immunoglobulin superfamily, containing an extracellular region of two Ig-like domains. The IgG binding site of human Fc gamma RII has been localized to an 8-amino acid segment of the second extracellular domain, Asn154-Ser161. In this study, evidence is presented to suggest that domain 1 and two additional regions of domain 2 also contribute to the binding of IgG by Fc gamma RII. Chimeric receptors generated by exchanging the extracellular domains and segments of domain 2 between Fc gamma RII and the structurally related Fc epsilon RI alpha chain were used to demonstrate that substitution of domain 1 in its entirety or the domain 2 regions encompassing residues Ser109-Val116 and Ser130-Thr135 resulted in a loss of the ability of these receptors to bind hIgG1 in dimeric form. Site-directed mutagenesis performed on individual residues within and flanking the Ser109-Val116 and Ser130-Thr135 domain 2 segments indicated that substitution of Lys113, Pro114, Leu115, Val116, Phe129, and His131 profoundly decreased the binding of hIgG1, whereas substitution of Asp133 and Pro134 increased binding. These findings suggest that not only is domain 1 contributing to the affinity of IgG binding by Fc gamma RII but, importantly, that the domain 2 regions Ser109-Val116 and Phe129-Thr135 also play key roles in the binding of hIgG1. The location of these binding regions on a molecular model of the entire extracellular region of Fc gamma RII indicates that they comprise loops that are juxtaposed in domain 2 at the interface with domain 1, with the putative crucial binding residues forming a hydrophobic pocket surrounded by a wall of predominantly aromatic and basic residues.
Internal ID Number: 7673151
URI: http://ahro.austin.org.au/austinjspui/handle/1/13073
URL: http://www.ncbi.nlm.nih.gov/pubmed/7673151
Type: Journal Article
Subjects: Animals
Base Sequence
Binding Sites
Cell Line
DNA, Complementary
Humans
Immunoglobulin G.metabolism
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Receptors, IgG.chemistry.metabolism
Recombinant Fusion Proteins.chemistry.metabolism
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.