8OYX

De novo designed soluble GPCR-like fold GLF_18

8OYX の概要

• エントリーDOI: 10.2210/pdb8oyx/pdb
• 分子名称: De novo designed soluble GPCR-like protein, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: gpcr, solubilized, de novo designed, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55655.54

構造登録者

Pacesa, M.,Correia, B.E. (登録日: 2023-05-05, 公開日: 2023-10-18, 最終更新日: 2024-08-14)

主引用文献

Goverde, C.A.,Pacesa, M.,Goldbach, N.,Dornfeld, L.J.,Balbi, P.E.M.,Georgeon, S.,Rosset, S.,Kapoor, S.,Choudhury, J.,Dauparas, J.,Schellhaas, C.,Kozlov, S.,Baker, D.,Ovchinnikov, S.,Vecchio, A.J.,Correia, B.E.
Computational design of soluble and functional membrane protein analogues.
Nature, 631:449-458, 2024

PubMed Abstract: De novo design of complex protein folds using solely computational means remains a substantial challenge. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, such as those from G-protein-coupled receptors, are not found in the soluble proteome, and we demonstrate that their structural features can be recapitulated in solution. Biophysical analyses demonstrate the high thermal stability of the designs, and experimental structures show remarkable design accuracy. The soluble analogues were functionalized with native structural motifs, as a proof of concept for bringing membrane protein functions to the soluble proteome, potentially enabling new approaches in drug discovery. In summary, we have designed complex protein topologies and enriched them with functionalities from membrane proteins, with high experimental success rates, leading to a de facto expansion of the functional soluble fold space.

PubMed: 38898281
DOI: 10.1038/s41586-024-07601-y

実験手法

X-RAY DIFFRACTION (2.11 Å)