6YWC

De novo designed protein 4E1H_95 in complex with 101F antibody

6YWC の概要

• エントリーDOI: 10.2210/pdb6ywc/pdb
• 分子名称: Antibody 101F, Heavy Chain, Antibody 101F, light chain, De novo design 4E1H_95, ... (4 entities in total)
• 機能のキーワード: de novo designed protein, de novo protein
• 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: 121449.93

構造登録者

Yang, C.,Sesterhenn, F.,Pojer, F.,Correia, B.E. (登録日: 2020-04-29, 公開日: 2020-10-07, 最終更新日: 2024-01-24)

主引用文献

Yang, C.,Sesterhenn, F.,Bonet, J.,van Aalen, E.A.,Scheller, L.,Abriata, L.A.,Cramer, J.T.,Wen, X.,Rosset, S.,Georgeon, S.,Jardetzky, T.,Krey, T.,Fussenegger, M.,Merkx, M.,Correia, B.E.
Bottom-up de novo design of functional proteins with complex structural features.
Nat.Chem.Biol., 17:492-500, 2021

PubMed Abstract: De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structures. Here, we used a bottom-up approach to build de novo proteins tailored to accommodate structurally complex functional motifs. We applied the bottom-up strategy to successfully design five folds for four distinct binding motifs, including a bifunctionalized protein with two motifs. Crystal structures confirmed the atomic-level accuracy of the computational designs. These de novo proteins were functional as components of biosensors to monitor antibody responses and as orthogonal ligands to modulate synthetic signaling receptors in engineered mammalian cells. Our work demonstrates the potential of bottom-up approaches to accommodate complex structural motifs, which will be essential to endow de novo proteins with elaborate biochemical functions, such as molecular recognition or catalysis.

PubMed: 33398169
DOI: 10.1038/s41589-020-00699-x

実験手法

X-RAY DIFFRACTION (2.85 Å)