9F8Y

Crystal structure of a designed three-motif Respiratory Syncytial Virus immunogen

9F8Y の概要

• エントリーDOI: 10.2210/pdb9f8y/pdb
• 分子名称: RSVF-multi-3.5 designed scaffold (2 entities in total)
• 機能のキーワード: designed immunogen, specific binding, rsv f protein, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67388.94

構造登録者

Castro, K.M.,Correia, B.E. (登録日: 2024-05-07, 公開日: 2025-05-21, 最終更新日: 2026-04-15)

主引用文献

Castro, K.M.,Watson, J.L.,Wang, J.,Southern, J.,Ayardulabi, R.,Georgeon, S.,Rosset, S.,Baker, D.,Correia, B.E.
Accurate single-domain scaffolding of three nonoverlapping protein epitopes using deep learning.
Nat.Chem.Biol., 22:604-611, 2026

PubMed Abstract: De novo protein design has seen major success in scaffolding single functional motifs; however, in nature, most proteins present multiple functional sites. Here, we describe an approach to simultaneously scaffold multiple functional sites in a single-domain protein using deep learning. We designed small single-domain immunogens, under 130 residues, that present three distinct and irregular motifs from respiratory syncytial virus. These motifs together comprise nearly half of the designed proteins; hence, the overall folds are quite unusual with little global similarity to proteins in the Protein Data Bank. Despite this, X-ray crystal structures confirmed the accuracy of presentation of each of the motifs and the multiepitope design yields improved cross-reactive titers and neutralizing response compared to a single-epitope immunogen. The successful presentation of three distinct binding surfaces in a small single-domain protein highlights the power of generative deep learning methods to solve complex protein design problems.

PubMed: 41350440
DOI: 10.1038/s41589-025-02083-z

実験手法

X-RAY DIFFRACTION (2.3 Å)