Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity

Abstract Computational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificial β-trefoil lectin that recognises Burkitt’s lymphoma cells, and which was designed with th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Daiki Terada, Arnout R. D. Voet, Hiroki Noguchi, Kenichi Kamata, Mio Ohki, Christine Addy, Yuki Fujii, Daiki Yamamoto, Yasuhiro Ozeki, Jeremy R. H. Tame, Kam Y. J. Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a440be7c963c4aa4b4ba9fc614b1d221
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a440be7c963c4aa4b4ba9fc614b1d221
record_format	dspace
spelling	oai:doaj.org-article:a440be7c963c4aa4b4ba9fc614b1d2212021-12-02T15:06:19ZComputational design of a symmetrical β-trefoil lectin with cancer cell binding activity10.1038/s41598-017-06332-72045-2322https://doaj.org/article/a440be7c963c4aa4b4ba9fc614b1d2212017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06332-7https://doaj.org/toc/2045-2322Abstract Computational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificial β-trefoil lectin that recognises Burkitt’s lymphoma cells, and which was designed with the intention of finding a basis for novel cancer treatments or diagnostics. The new protein, called “Mitsuba”, is based on the structure of the natural shellfish lectin MytiLec-1, a member of a small lectin family that uses unique sequence motifs to bind α-D-galactose. The three subdomains of MytiLec-1 each carry one galactose binding site, and the 149-residue protein forms a tight dimer in solution. Mitsuba (meaning “three-leaf” in Japanese) was created by symmetry constraining the structure of a MytiLec-1 subunit, resulting in a 150-residue sequence that contains three identical tandem repeats. Mitsuba-1 was expressed and crystallised to confirm the X-ray structure matches the predicted model. Mitsuba-1 recognises cancer cells that express globotriose (Galα(1,4)Galβ(1,4)Glc) on the surface, but the cytotoxicity is abolished.Daiki TeradaArnout R. D. VoetHiroki NoguchiKenichi KamataMio OhkiChristine AddyYuki FujiiDaiki YamamotoYasuhiro OzekiJeremy R. H. TameKam Y. J. ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daiki Terada Arnout R. D. Voet Hiroki Noguchi Kenichi Kamata Mio Ohki Christine Addy Yuki Fujii Daiki Yamamoto Yasuhiro Ozeki Jeremy R. H. Tame Kam Y. J. Zhang Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
description	Abstract Computational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificial β-trefoil lectin that recognises Burkitt’s lymphoma cells, and which was designed with the intention of finding a basis for novel cancer treatments or diagnostics. The new protein, called “Mitsuba”, is based on the structure of the natural shellfish lectin MytiLec-1, a member of a small lectin family that uses unique sequence motifs to bind α-D-galactose. The three subdomains of MytiLec-1 each carry one galactose binding site, and the 149-residue protein forms a tight dimer in solution. Mitsuba (meaning “three-leaf” in Japanese) was created by symmetry constraining the structure of a MytiLec-1 subunit, resulting in a 150-residue sequence that contains three identical tandem repeats. Mitsuba-1 was expressed and crystallised to confirm the X-ray structure matches the predicted model. Mitsuba-1 recognises cancer cells that express globotriose (Galα(1,4)Galβ(1,4)Glc) on the surface, but the cytotoxicity is abolished.
format	article
author	Daiki Terada Arnout R. D. Voet Hiroki Noguchi Kenichi Kamata Mio Ohki Christine Addy Yuki Fujii Daiki Yamamoto Yasuhiro Ozeki Jeremy R. H. Tame Kam Y. J. Zhang
author_facet	Daiki Terada Arnout R. D. Voet Hiroki Noguchi Kenichi Kamata Mio Ohki Christine Addy Yuki Fujii Daiki Yamamoto Yasuhiro Ozeki Jeremy R. H. Tame Kam Y. J. Zhang
author_sort	Daiki Terada
title	Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
title_short	Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
title_full	Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
title_fullStr	Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
title_full_unstemmed	Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
title_sort	computational design of a symmetrical β-trefoil lectin with cancer cell binding activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a440be7c963c4aa4b4ba9fc614b1d221
work_keys_str_mv	AT daikiterada computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT arnoutrdvoet computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT hirokinoguchi computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT kenichikamata computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT mioohki computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT christineaddy computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT yukifujii computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT daikiyamamoto computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT yasuhiroozeki computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT jeremyrhtame computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity AT kamyjzhang computationaldesignofasymmetricalbtrefoillectinwithcancercellbindingactivity
_version_	1718388534436429824

Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity

Ejemplares similares