6MJ3

CRYSTAL STRUCTURE OF RHESUS MACAQUE (MACACA MULATTA) IGG1 Fc Fragment-Fc-GAMMA RECEPTOR III complex

Summary for 6MJ3

• Entry DOI: 10.2210/pdb6mj3/pdb
• Descriptor: Igg1 Fc, Low affinity immunoglobulin gamma Fc region receptor III, 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, ... (4 entities in total)
• Functional Keywords: immunoglobulin, igg1, immune system, immunoglobulin-like beta sandwich, fc fragment, fc gamma receptor iii
• Biological source: Macaca mulatta (Rhesus macaque); More
• Total number of polymer chains: 6
• Total formula weight: 151068.07

Authors

Gohain, N.,Tolbert, W.D.,Pazgier, M. (deposition date: 2018-09-20, release date: 2019-08-21, Last modification date: 2023-10-18)

Primary citation

Tolbert, W.D.,Gohain, N.,Kremer, P.G.,Hederman, A.P.,Nguyen, D.N.,Van, V.,Sherburn, R.,Lewis, G.K.,Finzi, A.,Pollara, J.,Ackerman, M.E.,Barb, A.W.,Pazgier, M.
Decoding human-macaque interspecies differences in Fc-effector functions: The structural basis for CD16-dependent effector function in Rhesus macaques.
Front Immunol, 13:960411-960411, 2022

PubMed Abstract: Fc mediated effector functions of antibodies play important roles in immunotherapies and vaccine efficacy but assessing those functions in animal models can be challenging due to species differences. Rhesus macaques, (Mm) share approximately 93% sequence identity with humans but display important differences in their adaptive immune system that complicates their use in validating therapeutics and vaccines that rely on Fc effector functions. In contrast to humans, macaques only have one low affinity FcγRIII receptor, CD16, which shares a polymorphism at position 158 with human FcγRIIIa with Ile and Val variants. Here we describe structure-function relationships of the Ile/Val polymorphism in Mm FcγRIII. Our data indicate that the affinity of the allelic variants of Mm FcγRIII for the macaque IgG subclasses vary greatly with changes in glycan composition both on the Fc and the receptor. However, unlike the human Phe/Val polymorphism in FcγRIIIa, the higher affinity variant corresponds to the larger, more hydrophobic side chain, Ile, even though it is not directly involved in the binding interface. Instead, this side chain appears to modulate glycan-glycan interactions at the Fc/FcγRIII interface. Furthermore, changes in glycan composition on the receptor have a greater effect for the Val variant such that with oligomannose type glycans and with glycans only on Asn and Asn, Val becomes the variant with higher affinity to Fc. These results have implications not only for the better interpretation of nonhuman primate studies but also for studies performed with human effector cells carrying different FcγRIIIa alleles.

PubMed: 36131913
DOI: 10.3389/fimmu.2022.960411

Experimental method

X-RAY DIFFRACTION (3.8 Å)