6D4N

Crystal structure of a Fc fragment of Rhesus macaque (Macaca mulatta) IgG4

6D4N の概要

• エントリーDOI: 10.2210/pdb6d4n/pdb
• 関連するPDBエントリー: 4C54
• 分子名称: Fc fragment of IgG4, 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 (2 entities in total)
• 機能のキーワード: immunoglobulin, igg4, immune system, immunoglobulin-like beta sandwich, fc fragment
• 由来する生物種: Macaca mulatta
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53059.41

構造登録者

Gohain, N.,Tolbert, W.D.,Pazgier, M. (登録日: 2018-04-18, 公開日: 2019-05-01, 最終更新日: 2024-10-09)

主引用文献

Tolbert, W.D.,Subedi, G.P.,Gohain, N.,Lewis, G.K.,Patel, K.R.,Barb, A.W.,Pazgier, M.
From Rhesus macaque to human: structural evolutionary pathways for immunoglobulin G subclasses.
Mabs, 11:709-724, 2019

PubMed Abstract: The Old World monkey, Rhesus macaque (Macaca mulatta, Mm), is frequently used as a primate model organism in the study of human disease and to test new vaccines/antibody treatments despite diverging before chimpanzees and orangutans. Mm and humans share 93% genome identity with substantial differences in the genes of the adaptive immune system that lead to different functional IgG subclass characteristics, Fcγ receptors expressed on innate immune cells, and biological interactions. These differences put limitations on Mm use as a primary animal model in the study of human disease and to test new vaccines/antibody treatments. Here, we comprehensively analyzed molecular properties of the Fc domain of the four IgG subclasses of Rhesus macaque to describe potential mechanisms for their interactions with effector cell Fc receptors. Our studies revealed less diversity in the overall structure among the Mm IgG Fc, with MmIgG1 Fc being the most structurally like human IgG3, although its C2 loops and N glycan mobility are comparable to human IgG1. Furthermore, the Fcs of Mm IgG3 and 4 lack the structural properties typical for their human orthologues that determine IgG3's reduced interaction with the neonatal receptor and IgG4's ability for Fab-arm exchange and its weaker Fcγ receptor interactions. Taken together, our data indicate that MmIgG1-4 are less structurally divergent than the human IgGs, with only MmIgG1 matching the molecular properties of human IgG1 and 3, the most active IgGs in terms of Fcγ receptor binding and Fc-mediated functions. PDB accession numbers for deposited structures are 6D4E, 6D4I, 6D4M, and 6D4N for MmIgG1 Fc, MmIgG2 Fc, MmIgG3 Fc, and MmIgG4 Fc, respectively.

PubMed: 30939981
DOI: 10.1080/19420862.2019.1589852

実験手法

X-RAY DIFFRACTION (3.25 Å)