6QIO
Ternary complex of FcRn ectodomain, FcRn binding optimised human serum albumin and the human growth hormone derivative somapacitan
Summary for 6QIO
| Entry DOI | 10.2210/pdb6qio/pdb |
| Descriptor | Serum albumin, IgG receptor FcRn large subunit p51, Beta-2-microglobulin, ... (7 entities in total) |
| Functional Keywords | complex, albumin binding, long-acting growth hormone, somapacitan, hormone |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 111088.23 |
| Authors | Johansson, E. (deposition date: 2019-01-21, release date: 2020-02-05, Last modification date: 2024-10-09) |
| Primary citation | Johansson, E.,Nielsen, A.D.,Demuth, H.,Wiberg, C.,Schjodt, C.B.,Huang, T.,Chen, J.,Jensen, S.,Petersen, J.,Thygesen, P. Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative. Biochemistry, 59:1410-1419, 2020 Cited by PubMed Abstract: Somapacitan, a human growth hormone derivative that binds reversibly to albumin, was investigated for human serum albumin (HSA) and HSA domain binding. Isothermal titration calorimetry (ITC) binding profiles showed high-affinity binding (∼100-1000 nM) of one somapacitan molecule and low-affinity binding (∼1000-10000 nM) of one to two somapacitan molecules to HSA. The high-affinity site was identified in HSA domain III using size exclusion chromatography (SEC) and ITC. SEC studies showed that the neonatal Fc receptor shields one binding site for somapacitan, indicating its position in domain III. A crystal structure of somapacitan in complex with HSA optimized for neonatal Fc receptor binding, having four amino acid residue replacements, identified a low-affinity site in fatty acid-binding site 6 (domain II). Surface plasmon resonance (SPR) showed these replacements affect the kinetics of the high-affinity binding site. Furthermore, small-angle X-ray scattering and SPR brace two somapacitan-binding sites on HSA. PubMed: 32208682DOI: 10.1021/acs.biochem.0c00019 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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