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Design, structure a...
Design, structure and plasma binding of ancestral β-CoV scaffold antigens
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- Syrén, Per-Olof (author)
- KTH,Ytbehandlingsteknik,Chemistry For Life Science
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- Hueting, David A. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Chemistry For Life Science
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- Schriever, Karen (author)
- KTH,Science for Life Laboratory, SciLifeLab,Chemistry For Life Science
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- Zuo, Fanglei (author)
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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- Du, Likun (author)
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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- Persson, Helena (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Hofström, Camilla (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Ohlin, Mats (author)
- Drug Discovery and Development platform, Science for Life Laboratory, Sweden; Department of Immunotechnology, Lund University, Lund, Sweden
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- Walldén, Karin (author)
- Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Stockholm University, Stockholm, Sweden
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- Hammarström, Lennart (author)
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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- Marcotte, Harold (author)
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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- Pan Hammarström, Qiang (author)
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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- Andréll, Juni (author)
- Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Stockholm University, Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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(creator_code:org_t)
- Research Square Platform LLC, 2024
- English.
- Related links:
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https://doi.org/10.2...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Subject headings
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- The pandemic caused by Severe acute respiratory syndrome coronavirus 2 has had devastating consequences on global health and economy. Despite the success of vaccination campaigns emerging variants are of concern and novel viruses with the potential to drive future pandemics are circulating in nature. Development of vaccines can be challenging, as key viral protein antigens can be unstable or aggregate. In this study, we present the application of ancestral sequence reconstruction on coronavirus spike protein, resulting in stable and highly soluble ancestral scaffold antigens (AnSAs). The AnSAs interacted with plasma of patients recovered from COVID-19 but did not bind to the human angiotensin-converting enzyme 2 (ACE2) receptor. Cryo-EM analysis of the AnSAs yielded 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. This captured closed state is stabilised by an intricate hydrogen‑bonding network mediated by well-resolved loops, both within and across monomers, tethering the N‑terminal domain and RBD together, which determines their relative spatial orientation. Finally, we show how AnSAs are potent scaffolds by replacing the ancestral RBD with the Wuhan wild-type sequence, which restored ACE2 binding and increased the interaction with convalescent plasma. In contrast to rational antigen design depending on prior structural knowledge, our work highlights how stable and potentially interesting antigens can be generated using exclusively available sequence information.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Publication and Content Type
- vet (subject category)
- ovr (subject category)
To the university's database
- By the author/editor
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Syrén, Per-Olof
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Hueting, David A ...
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Schriever, Karen
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Zuo, Fanglei
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Du, Likun
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Persson, Helena
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show more...
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Hofström, Camill ...
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Ohlin, Mats
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Walldén, Karin
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Hammarström, Len ...
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Marcotte, Harold
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Pan Hammarström, ...
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Andréll, Juni
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- By the university
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Royal Institute of Technology