Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.

The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To i...

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Autores principales:	Annalisa Nuccitelli, C Daniela Rinaudo, Barbara Brogioni, Roberta Cozzi, Mario Ferrer-Navarro, Daniel Yero, John L Telford, Guido Grandi, Xavier Daura, Martin Zacharias, Domenico Maione
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c214f3573e9e49aabd3daa62b2b5b92d
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spelling	oai:doaj.org-article:c214f3573e9e49aabd3daa62b2b5b92d2021-11-18T05:52:03ZUnderstanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.1553-734X1553-735810.1371/journal.pcbi.1003115https://doaj.org/article/c214f3573e9e49aabd3daa62b2b5b92d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23825940/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response.Annalisa NuccitelliC Daniela RinaudoBarbara BrogioniRoberta CozziMario Ferrer-NavarroDaniel YeroJohn L TelfordGuido GrandiXavier DauraMartin ZachariasDomenico MaionePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 6, p e1003115 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Annalisa Nuccitelli C Daniela Rinaudo Barbara Brogioni Roberta Cozzi Mario Ferrer-Navarro Daniel Yero John L Telford Guido Grandi Xavier Daura Martin Zacharias Domenico Maione Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.
description	The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response.
format	article
author	Annalisa Nuccitelli C Daniela Rinaudo Barbara Brogioni Roberta Cozzi Mario Ferrer-Navarro Daniel Yero John L Telford Guido Grandi Xavier Daura Martin Zacharias Domenico Maione
author_facet	Annalisa Nuccitelli C Daniela Rinaudo Barbara Brogioni Roberta Cozzi Mario Ferrer-Navarro Daniel Yero John L Telford Guido Grandi Xavier Daura Martin Zacharias Domenico Maione
author_sort	Annalisa Nuccitelli
title	Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.
title_short	Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.
title_full	Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.
title_fullStr	Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.
title_full_unstemmed	Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.
title_sort	understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group b streptococcus.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c214f3573e9e49aabd3daa62b2b5b92d
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Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus.

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