6M58

Crystal structure of a complex between human serum albumin and the antibody Fab SL335

6M58 の概要

• エントリーDOI: 10.2210/pdb6m58/pdb
• 分子名称: Serum albumin, Heavy chain of the SL335 antibody fab, Light chain of the SL335 antibody Fab, ... (4 entities in total)
• 機能のキーワード: serum albumin, anti-albumin, antibody fab, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 228362.70

構造登録者

Cho, S.Y.,Yoon, S.I. (登録日: 2020-03-10, 公開日: 2020-04-29, 最終更新日: 2024-10-30)

主引用文献

Cho, S.Y.,Han, J.,Cha, S.H.,Yoon, S.I.
Structural basis of serum albumin recognition by SL335, an antibody Fab extending the serum half-life of protein therapeutics.
Biochem.Biophys.Res.Commun., 526:941-946, 2020

PubMed Abstract: Human serum albumin (HSA) has been used to extend the serum half-lives of various protein therapeutics through genetic fusion because HSA exhibits an exceptionally long circulation time as a result of neonatal Fc receptor (FcRn)-mediated recycling. As another serum half-life extender, the human antibody Fab SL335 that strongly binds HSA was developed. When SL335 was fused to a protein therapeutic, SL335 was shown to prolong the half-life of the drug. Despite the significance of SL335-HSA binding in the extension of drug circulation time, it remains unclear how SL335 interacts with HSA at a molecular structural level. To reveal the structural basis of HSA recognition by SL335, we determined the crystal structure of the SL335-HSA complex at a resolution of 2.95 Å. SL335 binds HSA at a 1:1 stoichiometry. SL335 uses the exposed loops of its heavy and light chains to specifically recognize the IIa and IIb subdomains of HSA. The SL335 epitope is located on the opposite side of the FcRn-binding site and does not overlap with it, suggesting that SL335 extends the serum half-lives of itself and its fusion partner through an FcRn-dependent recycling mechanism.

PubMed: 32284170
DOI: 10.1016/j.bbrc.2020.03.133

実験手法

X-RAY DIFFRACTION (2.95 Å)