8DJ7

The complex structure between human IgG1 Fc and its high affinity receptor FcgRI H174R variant

Summary for 8DJ7

• Entry DOI: 10.2210/pdb8dj7/pdb
• Descriptor: Ig gamma-1 Fc chain, High affinity immunoglobulin gamma Fc receptor I, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: high affinity igg1 fc receptor, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 83880.19

Authors

Lu, J.,Sun, P.D. (deposition date: 2022-06-30, release date: 2023-05-10, Last modification date: 2023-10-25)

Primary citation

Lu, J.,Spencer, M.,Zou, Z.,Traver, M.,Brzostowski, J.,Sun, P.D.
Fc gamma RI FG-loop functions as a pH sensitive switch for IgG binding and release.
Front Immunol, 14:1100499-1100499, 2023

PubMed Abstract: Understanding the molecular mechanism underlying the hierarchic binding between FcγRs and IgG antibodies is critical for therapeutic antibody engineering and FcγR functions. The recent determination of crystal structures of FcγRI-Fc complexes, however, resulted in two controversial mechanisms for the high affinity receptor binding to IgG. Here, we describe high resolution structures of a bovine FG-loop variant of FcγRI in complex with the Fc fragment of IgG crystallized in three different conditions at neutral pH, confirming the characteristic FG loop-Fc interaction is critical to the high affinity immunoglobulin binding. We showed that the FcγRI D2-domain FG-loop functioned as a pH-sensing switch for IgG binding. Further live cell imaging of FcγRI-mediated internalization of immune complexes showed a pH sensitive temporal-spatial antibody-antigen uptake and release. Taken together, we demonstrate that the structures of FcγRI-Fc crystallized at neutral and acidic pH, respectively, represent the high and low affinity binding states of the receptor for IgG uptake and release. These results support a role for FcγRI in antigen delivery, highlight the importance of Fc glycan in antibody binding to the high affinity receptor and provide new insights to future antibody engineering.

PubMed: 36814926
DOI: 10.3389/fimmu.2023.1100499

Experimental method

X-RAY DIFFRACTION (2.39 Å)