4B7I
Crystal Structure of Human IgG Fc Bearing Hybrid-type Glycans
Summary for 4B7I
| Entry DOI | 10.2210/pdb4b7i/pdb |
| Related | 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 |
| Descriptor | 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) |
| Functional Keywords | immune system, igg, antibody, swainsonine, hybrid |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 2 |
| Total formula weight | 51052.66 |
| Authors | 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. (deposition date: 2012-08-20, release date: 2012-10-17, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 23025485DOI: 10.1021/JA306068G PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.36 Å) |
Structure validation
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