7XRZ

Crystal structure of BRIL and SRP2070_Fab complex

7XRZ の概要

• エントリーDOI: 10.2210/pdb7xrz/pdb
• 分子名称: IGG LIGHT CHAIN, IGG HEAVY CHAIN, Soluble cytochrome b562, ... (4 entities in total)
• 機能のキーワード: bril, antibody, complex, immune system
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 118697.93

構造登録者

Suzuki, M.,Miyagi, H.,Yasunaga, M.,Asada, H.,Iwata, S.,Saito, J. (登録日: 2022-05-12, 公開日: 2023-05-10, 最終更新日: 2024-10-16)

主引用文献

Miyagi, H.,Suzuki, M.,Yasunaga, M.,Asada, H.,Iwata, S.,Saito, J.I.
Structural insight into an anti-BRIL Fab as a G-protein-coupled receptor crystallization chaperone.
Acta Crystallogr D Struct Biol, 79:435-441, 2023

PubMed Abstract: Structure determination of G-protein-coupled receptors (GPCRs) is key for the successful development of efficient drugs targeting GPCRs. BRIL is a thermostabilized apocytochrome b (with M7W/H102I/R106L mutations) from Escherichia coli and is often used as a GPCR fusion protein for expression and crystallization. SRP2070Fab, an anti-BRIL antibody Fab fragment, has been reported to facilitate and enhance the crystallization of BRIL-fused GPCRs as a crystallization chaperone. This study was conducted to characterize the high-resolution crystal structure of the BRIL-SRP2070Fab complex. The structure of the BRIL-SRP2070Fab complex was determined at 2.1 Å resolution. This high-resolution structure elucidates the binding interaction between BRIL and SRP2070Fab. When binding to BRIL, SRP2070Fab recognizes conformational epitopes, not linear epitopes, on the surface of BRIL helices III and IV, thereby binding perpendicularly to the helices, which indicates stable binding. Additionally, the packing contacts of the BRIL-SRP2070Fab co-crystal are largely due to SRP2070Fab rather than BRIL. The accumulation of SRP2070Fab molecules by stacking is remarkable and is consistent with the finding that stacking of SRP2070Fab is predominant in known crystal structures of BRIL-fused GPCRs complexed with SRP2070Fab. These findings clarified the mechanism of SRP2070Fab as a crystallization chaperone. Moreover, these data will be useful in the structure-based drug design of membrane-protein drug targets.

PubMed: 37098908
DOI: 10.1107/S205979832300311X

実験手法

X-RAY DIFFRACTION (2.1 Å)