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-Structure paper
タイトル | Design, structure and plasma binding of ancestral β-CoV scaffold antigens. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 6527, Year 2023 |
掲載日 | 2023年10月16日 |
著者 | David Hueting / Karen Schriever / Rui Sun / Stelios Vlachiotis / Fanglei Zuo / Likun Du / Helena Persson / Camilla Hofström / Mats Ohlin / Karin Walldén / Marcus Buggert / Lennart Hammarström / Harold Marcotte / Qiang Pan-Hammarström / Juni Andréll / Per-Olof Syrén / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:37845250 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.59 - 2.77 Å |
構造データ | EMDB-15475, PDB-8aja: EMDB-15482, PDB-8ajl: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | BIOSYNTHETIC PROTEIN / Ancestor / Spike / Coronavirus / Scaffold / S-protein / Protein Engineering |