4B7I

Crystal Structure of Human IgG Fc Bearing Hybrid-type Glycans

4B7I の概要

• エントリーDOI: 10.2210/pdb4b7i/pdb
• 関連するPDBエントリー: 1AJ7 1AQK 1BEY 1D5B 1D5I 1D6V 1DN2 1E4K 1FC1 1FC2 1FCC 1H3T 1H3U 1H3V 1H3W 1H3Y 1I7Z 1L6X 1OQX 1T83 1T89 2IWG 2J6E 2RCS 2WAH 4ACP
• 分子名称: IG GAMMA-1 CHAIN C REGION, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]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, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: immune system, igg, antibody, swainsonine, hybrid
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51052.66

構造登録者

Bowden, T.A.,Baruah, K.,Coles, C.H.,Harvey, D.J.,Song, B.D.,Stuart, D.I.,Aricescu, A.R.,Scanlan, C.N.,Jones, E.Y.,Crispin, M. (登録日: 2012-08-20, 公開日: 2012-10-17, 最終更新日: 2024-11-13)

主引用文献

Bowden, T.A.,Baruah, K.,Coles, C.H.,Harvey, D.J.,Yu, X.,Song, B.D.,Stuart, D.I.,Aricescu, A.R.,Scanlan, C.N.,Jones, E.Y.,Crispin, M.
Chemical and Structural Analysis of an Antibody Folding Intermediate Trapped During Glycan Biosynthesis.
J.Am.Chem.Soc., 134:17554-, 2012

PubMed Abstract: Human IgG Fc glycosylation modulates immunological effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. Engineering of Fc glycans therefore enables fine-tuning of the therapeutic properties of monoclonal antibodies. The N-linked glycans of Fc are typically complex-type, forming a network of noncovalent interactions along the protein surface of the Cγ2 domain. Here, we manipulate the mammalian glycan-processing pathway to trap IgG1 Fc at sequential stages of maturation, from oligomannose- to hybrid- to complex-type glycans, and show that the Fc is structurally stabilized following the transition of glycans from their hybrid- to complex-type state. X-ray crystallographic analysis of this hybrid-type intermediate reveals that N-linked glycans undergo conformational changes upon maturation, including a flip within the trimannosyl core. Our crystal structure of this intermediate reveals a molecular basis for antibody biogenesis and provides a template for the structure-guided engineering of the protein-glycan interface of therapeutic antibodies.

PubMed: 23025485
DOI: 10.1021/JA306068G

実験手法

X-RAY DIFFRACTION (2.36 Å)