Search: id:"swepub:oai:DiVA.org:su-145997" >
Engineered botulinu...
Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-07-03
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Springer Science and Business Media LLC,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-145997
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-145997URI
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https://doi.org/10.1038/s41467-017-00064-yDOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-137788URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Botulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because of a residue difference. Increasing the binding affinity to h-Syt II may improve botulinum neurotoxin B's therapeutic efficacy and reduce adverse effects. Here we utilized the bacterial adenylate cyclase two-hybrid method and carried out a saturation mutagenesis screen in the Syt II-binding pocket of botulinum neurotoxin B. The screen identifies E1191 as a key residue: replacing it with M/C/V/Q enhances botulinum neurotoxin B binding to human synaptotagmin II. Adding S1199Y/W or W1178Q as a secondary mutation further increases binding affinity. Mutant botulinum neurotoxin B containing E1191M/S1199Y exhibits similar to 11-fold higher efficacy in blocking neurotransmission than wild-type botulinum neurotoxin B in neurons expressing human synaptotagmin II, demonstrating that enhancing receptor binding increases the overall efficacy at functional levels. The engineered botulinum neurotoxin B provides a platform to develop therapeutic toxins with improved efficacy.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Peng, Lisheng
(author)
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Berntsson, Ronnie P. -A.Umeå universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Umeå University, Sweden,Institutionen för medicinsk kemi och biofysik,Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden(Swepub:umu)robe0049
(author)
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Liu, Sai Man
(author)
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Park, SunHyun
(author)
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Yu, Feifan
(author)
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Boone, Christopher
(author)
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Palan, Shilpa
(author)
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Beard, Matthew
(author)
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Chabrier, Pierre-Etienne
(author)
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Stenmark, PålStockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)stenm
(author)
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Krupp, Johannes
(author)
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Dong, Min
(author)
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Stockholms universitetInstitutionen för biokemi och biofysik
(creator_code:org_t)
Related titles
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In:Nature Communications: Springer Science and Business Media LLC82041-1723
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Tao, Liang
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Peng, Lisheng
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Berntsson, Ronni ...
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Liu, Sai Man
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Park, SunHyun
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Yu, Feifan
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Boone, Christoph ...
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Palan, Shilpa
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Beard, Matthew
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Chabrier, Pierre ...
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Stenmark, Pål
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Krupp, Johannes
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Dong, Min
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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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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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Nature Communica ...
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Stockholm University
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Umeå University