Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design

Certain bovine antibodies have ultra-long long complementarity-determining regions (CDRs) that contain a knob for antigen interaction, which is connected to the antibody through a stalk. Here, the authors combine biophysical experiments and MD simulations and show that the stalk length is critical f...

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Autores principales:	Hristo L. Svilenov, Julia Sacherl, Ulrike Protzer, Martin Zacharias, Johannes Buchner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/551d369430b84beb8602ae26a8e6b65f
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spelling	oai:doaj.org-article:551d369430b84beb8602ae26a8e6b65f2021-11-21T12:36:26ZMechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design10.1038/s41467-021-27103-z2041-1723https://doaj.org/article/551d369430b84beb8602ae26a8e6b65f2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-27103-zhttps://doaj.org/toc/2041-1723Certain bovine antibodies have ultra-long long complementarity-determining regions (CDRs) that contain a knob for antigen interaction, which is connected to the antibody through a stalk. Here, the authors combine biophysical experiments and MD simulations and show that the stalk length is critical for the folding and stability of these antibodies. The authors also demonstrate that ultra-long bovine CDRs can be grafted into human antibodies, and furthermore show that de novo designed mini-domains that bind to the SARS-CoV-2 spike protein with high affinity can be integrated as a knob in ultra-long CDRs in bovine and human antibodies, which neutralize SARS-CoV-2.Hristo L. SvilenovJulia SacherlUlrike ProtzerMartin ZachariasJohannes BuchnerNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Hristo L. Svilenov Julia Sacherl Ulrike Protzer Martin Zacharias Johannes Buchner Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design
description	Certain bovine antibodies have ultra-long long complementarity-determining regions (CDRs) that contain a knob for antigen interaction, which is connected to the antibody through a stalk. Here, the authors combine biophysical experiments and MD simulations and show that the stalk length is critical for the folding and stability of these antibodies. The authors also demonstrate that ultra-long bovine CDRs can be grafted into human antibodies, and furthermore show that de novo designed mini-domains that bind to the SARS-CoV-2 spike protein with high affinity can be integrated as a knob in ultra-long CDRs in bovine and human antibodies, which neutralize SARS-CoV-2.
format	article
author	Hristo L. Svilenov Julia Sacherl Ulrike Protzer Martin Zacharias Johannes Buchner
author_facet	Hristo L. Svilenov Julia Sacherl Ulrike Protzer Martin Zacharias Johannes Buchner
author_sort	Hristo L. Svilenov
title	Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design
title_short	Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design
title_full	Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design
title_fullStr	Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design
title_full_unstemmed	Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design
title_sort	mechanistic principles of an ultra-long bovine cdr reveal strategies for antibody design
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/551d369430b84beb8602ae26a8e6b65f
work_keys_str_mv	AT hristolsvilenov mechanisticprinciplesofanultralongbovinecdrrevealstrategiesforantibodydesign AT juliasacherl mechanisticprinciplesofanultralongbovinecdrrevealstrategiesforantibodydesign AT ulrikeprotzer mechanisticprinciplesofanultralongbovinecdrrevealstrategiesforantibodydesign AT martinzacharias mechanisticprinciplesofanultralongbovinecdrrevealstrategiesforantibodydesign AT johannesbuchner mechanisticprinciplesofanultralongbovinecdrrevealstrategiesforantibodydesign
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Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design

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