Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.

Lectin-glycan interactions facilitate inter- and intracellular communication in many processes including protein trafficking, host-pathogen recognition, and tumorigenesis promotion. Specific recognition of glycans by lectins is also the basis for a wide range of applications in areas including glyco...

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Autores principales:	Daniel E Mattox, Chris Bailey-Kellogg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8b0db8cc918b4f0cacf09f08ef43d34a
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spelling	oai:doaj.org-article:8b0db8cc918b4f0cacf09f08ef43d34a2021-11-25T05:40:32ZComprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.1553-734X1553-735810.1371/journal.pcbi.1009470https://doaj.org/article/8b0db8cc918b4f0cacf09f08ef43d34a2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009470https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Lectin-glycan interactions facilitate inter- and intracellular communication in many processes including protein trafficking, host-pathogen recognition, and tumorigenesis promotion. Specific recognition of glycans by lectins is also the basis for a wide range of applications in areas including glycobiology research, cancer screening, and antiviral therapeutics. To provide a better understanding of the determinants of lectin-glycan interaction specificity and support such applications, this study comprehensively investigates specificity-conferring features of all available lectin-glycan complex structures. Systematic characterization, comparison, and predictive modeling of a set of 221 complementary physicochemical and geometric features representing these interactions highlighted specificity-conferring features with potential mechanistic insight. Univariable comparative analyses with weighted Wilcoxon-Mann-Whitney tests revealed strong statistical associations between binding site features and specificity that are conserved across unrelated lectin binding sites. Multivariable modeling with random forests demonstrated the utility of these features for predicting the identity of bound glycans based on generalized patterns learned from non-homologous lectins. These analyses revealed global determinants of lectin specificity, such as sialic acid glycan recognition in deep, concave binding sites enriched for positively charged residues, in contrast to high mannose glycan recognition in fairly shallow but well-defined pockets enriched for non-polar residues. Focused fine specificity analysis of hemagglutinin interactions with human-like and avian-like glycans uncovered features representing both known and novel mutations related to shifts in influenza tropism from avian to human tissues. As the approach presented here relies on co-crystallized lectin-glycan pairs for studying specificity, it is limited in its inferences by the quantity, quality, and diversity of the structural data available. Regardless, the systematic characterization of lectin binding sites presented here provides a novel approach to studying lectin specificity and is a step towards confidently predicting new lectin-glycan interactions.Daniel E MattoxChris Bailey-KelloggPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 10, p e1009470 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Daniel E Mattox Chris Bailey-Kellogg Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
description	Lectin-glycan interactions facilitate inter- and intracellular communication in many processes including protein trafficking, host-pathogen recognition, and tumorigenesis promotion. Specific recognition of glycans by lectins is also the basis for a wide range of applications in areas including glycobiology research, cancer screening, and antiviral therapeutics. To provide a better understanding of the determinants of lectin-glycan interaction specificity and support such applications, this study comprehensively investigates specificity-conferring features of all available lectin-glycan complex structures. Systematic characterization, comparison, and predictive modeling of a set of 221 complementary physicochemical and geometric features representing these interactions highlighted specificity-conferring features with potential mechanistic insight. Univariable comparative analyses with weighted Wilcoxon-Mann-Whitney tests revealed strong statistical associations between binding site features and specificity that are conserved across unrelated lectin binding sites. Multivariable modeling with random forests demonstrated the utility of these features for predicting the identity of bound glycans based on generalized patterns learned from non-homologous lectins. These analyses revealed global determinants of lectin specificity, such as sialic acid glycan recognition in deep, concave binding sites enriched for positively charged residues, in contrast to high mannose glycan recognition in fairly shallow but well-defined pockets enriched for non-polar residues. Focused fine specificity analysis of hemagglutinin interactions with human-like and avian-like glycans uncovered features representing both known and novel mutations related to shifts in influenza tropism from avian to human tissues. As the approach presented here relies on co-crystallized lectin-glycan pairs for studying specificity, it is limited in its inferences by the quantity, quality, and diversity of the structural data available. Regardless, the systematic characterization of lectin binding sites presented here provides a novel approach to studying lectin specificity and is a step towards confidently predicting new lectin-glycan interactions.
format	article
author	Daniel E Mattox Chris Bailey-Kellogg
author_facet	Daniel E Mattox Chris Bailey-Kellogg
author_sort	Daniel E Mattox
title	Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
title_short	Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
title_full	Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
title_fullStr	Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
title_full_unstemmed	Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
title_sort	comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/8b0db8cc918b4f0cacf09f08ef43d34a
work_keys_str_mv	AT danielemattox comprehensiveanalysisoflectinglycaninteractionsrevealsdeterminantsoflectinspecificity AT chrisbaileykellogg comprehensiveanalysisoflectinglycaninteractionsrevealsdeterminantsoflectinspecificity
_version_	1718414528186679296

Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity.

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