The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding

Abstract Antibody research has traditionally focused on heavy chains, often neglecting the important complementary role of light chains in antibody formation and secretion. In the light chain, the complementarity-determining region 3 (VL-CDR3) is specifically implicated in disease states. By modulat...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chinh Tran-To Su, Wei-Li Ling, Wai-Heng Lua, Jun-Jie Poh, Samuel Ken-En Gan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eafe5b34846144f1ab33c00235d65039
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:eafe5b34846144f1ab33c00235d65039
record_format	dspace
spelling	oai:doaj.org-article:eafe5b34846144f1ab33c00235d650392021-12-02T16:06:14ZThe role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding10.1038/s41598-017-02756-32045-2322https://doaj.org/article/eafe5b34846144f1ab33c00235d650392017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02756-3https://doaj.org/toc/2045-2322Abstract Antibody research has traditionally focused on heavy chains, often neglecting the important complementary role of light chains in antibody formation and secretion. In the light chain, the complementarity-determining region 3 (VL-CDR3) is specifically implicated in disease states. By modulating VL-CDR3 exposure on the scaffold through deletions in the framework region 3 (VL-FWR3), we further investigated the effects on secretion in recombinant production and antigen binding kinetics. Our random deletions of two residues in the VL-FWR3 of a Trastuzumab model showed that the single deletions could impact recombinant production without significant effect on Her2 binding. When both the selected residues were deleted, antibody secretion was additively decreased, and so was Her2 binding kinetics. Interestingly, we also found allosteric effects on the Protein L binding site at VL-FWR1 elicited by these deletions in VL- FWR3. Together, these findings demonstrate the importance of light chain FWR3 in antigen binding, recombinant production, and antibody purification using Protein L.Chinh Tran-To SuWei-Li LingWai-Heng LuaJun-Jie PohSamuel Ken-En GanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chinh Tran-To Su Wei-Li Ling Wai-Heng Lua Jun-Jie Poh Samuel Ken-En Gan The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding
description	Abstract Antibody research has traditionally focused on heavy chains, often neglecting the important complementary role of light chains in antibody formation and secretion. In the light chain, the complementarity-determining region 3 (VL-CDR3) is specifically implicated in disease states. By modulating VL-CDR3 exposure on the scaffold through deletions in the framework region 3 (VL-FWR3), we further investigated the effects on secretion in recombinant production and antigen binding kinetics. Our random deletions of two residues in the VL-FWR3 of a Trastuzumab model showed that the single deletions could impact recombinant production without significant effect on Her2 binding. When both the selected residues were deleted, antibody secretion was additively decreased, and so was Her2 binding kinetics. Interestingly, we also found allosteric effects on the Protein L binding site at VL-FWR1 elicited by these deletions in VL- FWR3. Together, these findings demonstrate the importance of light chain FWR3 in antigen binding, recombinant production, and antibody purification using Protein L.
format	article
author	Chinh Tran-To Su Wei-Li Ling Wai-Heng Lua Jun-Jie Poh Samuel Ken-En Gan
author_facet	Chinh Tran-To Su Wei-Li Ling Wai-Heng Lua Jun-Jie Poh Samuel Ken-En Gan
author_sort	Chinh Tran-To Su
title	The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding
title_short	The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding
title_full	The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding
title_fullStr	The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding
title_full_unstemmed	The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding
title_sort	role of antibody vκ framework 3 region towards antigen binding: effects on recombinant production and protein l binding
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/eafe5b34846144f1ab33c00235d65039
work_keys_str_mv	AT chinhtrantosu theroleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT weililing theroleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT waihenglua theroleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT junjiepoh theroleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT samuelkenengan theroleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT chinhtrantosu roleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT weililing roleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT waihenglua roleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT junjiepoh roleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding AT samuelkenengan roleofantibodyvkframework3regiontowardsantigenbindingeffectsonrecombinantproductionandproteinlbinding
_version_	1718385063058472960

The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding

Ejemplares similares