5DK3
Crystal Structure of Pembrolizumab, a full length IgG4 antibody
Summary for 5DK3
| Entry DOI | 10.2210/pdb5dk3/pdb |
| Related PRD ID | PRD_900003 |
| Descriptor | Light Chain, Heavy Chain, 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)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | cancer, antibody, subclasses, igg4, melanoma, immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 4 |
| Total formula weight | 149953.56 |
| Authors | Scapin, G.,Prosise, W.,Reichert, P. (deposition date: 2015-09-02, release date: 2015-11-18, Last modification date: 2024-11-13) |
| Primary citation | Scapin, G.,Yang, X.,Prosise, W.W.,McCoy, M.,Reichert, P.,Johnston, J.M.,Kashi, R.S.,Strickland, C. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. Nat.Struct.Mol.Biol., 22:953-958, 2015 Cited by PubMed Abstract: Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc domain is glycosylated at the CH2 domain on both chains, but one CH2 domain is rotated 120° with respect to the conformation observed in all reported structures to date, and its glycan chain faces the solvent. We speculate that this new conformation is driven by the shorter hinge. The structure suggests a role for the S228P mutation in preventing the IgG4 arm exchange. In addition, this unusual Fc conformation suggests possible structural diversity between IgG subclasses and shows that use of isolated antibody fragments could mask potentially important interactions, owing to molecular flexibility. PubMed: 26595420DOI: 10.1038/nsmb.3129 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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