5JII
Crystal structure of human IgG1-Fc
Summary for 5JII
Entry DOI | 10.2210/pdb5jii/pdb |
Related | 5JIH 5JIK |
Descriptor | Ig gamma-1 chain C region, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-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, ... (6 entities in total) |
Functional Keywords | immune system, antibody, immunoglobulin g1, fc fragment, glycosylations |
Biological source | Homo sapiens (Human) |
Cellular location | Secreted : P01857 |
Total number of polymer chains | 2 |
Total formula weight | 52939.05 |
Authors | Humm, A.,Lobner, E.,Mlynek, G.,Obinger, C.,Djinovic-Carugo, K. (deposition date: 2016-04-22, release date: 2017-04-12, Last modification date: 2024-10-23) |
Primary citation | Lobner, E.,Humm, A.S.,Goritzer, K.,Mlynek, G.,Puchinger, M.G.,Hasenhindl, C.,Ruker, F.,Traxlmayr, M.W.,Djinovic-Carugo, K.,Obinger, C. Fcab-HER2 Interaction: a Menage a Trois. Lessons from X-Ray and Solution Studies. Structure, 25:878-889.e5, 2017 Cited by PubMed Abstract: The crystallizable fragment (Fc) of the immunoglobulin class G (IgG) is an attractive scaffold for the design of novel therapeutics. Upon engineering the C-terminal loops in the CH3 domains, Fcabs (Fc domain with antigen-binding sites) can be designed. We present the first crystal structures of Fcabs, i.e., of the HER2-binding clone H10-03-6 having the AB and EF loop engineered and the stabilized version STAB19 derived by directed evolution. Comparison with the crystal structure of the Fc wild-type protein reveals conservation of the overall domain structures but significant differences in EF-loop conformations. Furthermore, we present the first Fcab-antigen complex structures demonstrating the interaction between the engineered Fcab loops with domain IV of HER2. The crystal structures of the STAB19-HER2 and H10-03-6-HER2 complexes together with analyses by isothermal titration calorimetry, SEC-MALS, and fluorescence correlation spectroscopy show that one homodimeric Fcab binds two HER2 molecules following a negative cooperative binding behavior. PubMed: 28528777DOI: 10.1016/j.str.2017.04.014 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.79 Å) |
Structure validation
Download full validation report