8AJA

Structure of the Ancestral Scaffold Antigen-5 of Coronavirus Spike protein

8AJA の概要

• エントリーDOI: 10.2210/pdb8aja/pdb
• EMDBエントリー: 15475
• 分子名称: Spike glycoprotein,Fibritin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: ancestor, spike, coronavirus, scaffold, s-protein, protein engineering, biosynthetic protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 424084.55

構造登録者

Hueting, D.,Schriever, K.,Wallden, K.,Andrell, J.,Syren, P.O. (登録日: 2022-07-27, 公開日: 2023-08-16, 最終更新日: 2024-10-23)

主引用文献

Hueting, D.,Schriever, K.,Sun, R.,Vlachiotis, S.,Zuo, F.,Du, L.,Persson, H.,Hofstrom, C.,Ohlin, M.,Wallden, K.,Buggert, M.,Hammarstrom, L.,Marcotte, H.,Pan-Hammarstrom, Q.,Andrell, J.,Syren, P.O.
Design, structure and plasma binding of ancestral beta-CoV scaffold antigens.
Nat Commun, 14:6527-6527, 2023

PubMed Abstract: We report the application of ancestral sequence reconstruction on coronavirus spike protein, resulting in stable and highly soluble ancestral scaffold antigens (AnSAs). The AnSAs interact with plasma of patients recovered from COVID-19 but do not bind to the human angiotensin-converting enzyme 2 (ACE2) receptor. Cryo-EM analysis of the AnSAs yield high resolution structures (2.6-2.8 Å) indicating a closed pre-fusion conformation in which all three receptor-binding domains (RBDs) are facing downwards. The structures reveal an intricate hydrogen-bonding network mediated by well-resolved loops, both within and across monomers, tethering the N-terminal domain and RBD together. We show that AnSA-5 can induce and boost a broad-spectrum immune response against the wild-type RBD as well as circulating variants of concern in an immune organoid model derived from tonsils. Finally, we highlight how AnSAs are potent scaffolds by replacing the ancestral RBD with the wild-type sequence, which restores ACE2 binding and increases the interaction with convalescent plasma.

PubMed: 37845250
DOI: 10.1038/s41467-023-42200-x

実験手法

ELECTRON MICROSCOPY (2.59 Å)