6QIO

Ternary complex of FcRn ectodomain, FcRn binding optimised human serum albumin and the human growth hormone derivative somapacitan

6QIO の概要

• エントリーDOI: 10.2210/pdb6qio/pdb
• 分子名称: Serum albumin, IgG receptor FcRn large subunit p51, Beta-2-microglobulin, ... (7 entities in total)
• 機能のキーワード: complex, albumin binding, long-acting growth hormone, somapacitan, hormone
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 111088.23

構造登録者

Johansson, E. (登録日: 2019-01-21, 公開日: 2020-02-05, 最終更新日: 2024-10-09)

主引用文献

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

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: 32208682
DOI: 10.1021/acs.biochem.0c00019

実験手法

X-RAY DIFFRACTION (1.95 Å)