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Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae

Streptococcus pneumoniae scavenges essential zinc ions from the host during colonization and infection. This is achieved by the ATP-binding cassette transporter, AdcCB, and two solute-binding proteins (SBPs), AdcA and AdcAII. It has been established that AdcAII serves a greater role during initial i...

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Autores principales: Župan, Marina L., Luo, Zhenyao, Ganio, Katherine, Pederick, Victoria G., Neville, Stephanie L., Deplazes, Evelyne, Kobe, Boštjan, McDevitt, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416893/
https://www.ncbi.nlm.nih.gov/pubmed/34490149
http://dx.doi.org/10.3389/fcimb.2021.729981
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author Župan, Marina L.
Luo, Zhenyao
Ganio, Katherine
Pederick, Victoria G.
Neville, Stephanie L.
Deplazes, Evelyne
Kobe, Boštjan
McDevitt, Christopher A.
author_facet Župan, Marina L.
Luo, Zhenyao
Ganio, Katherine
Pederick, Victoria G.
Neville, Stephanie L.
Deplazes, Evelyne
Kobe, Boštjan
McDevitt, Christopher A.
author_sort Župan, Marina L.
collection PubMed
description Streptococcus pneumoniae scavenges essential zinc ions from the host during colonization and infection. This is achieved by the ATP-binding cassette transporter, AdcCB, and two solute-binding proteins (SBPs), AdcA and AdcAII. It has been established that AdcAII serves a greater role during initial infection, but the molecular details of how the protein selectively acquires Zn(II) remain poorly understood. This can be attributed to the refractory nature of metal-free AdcAII to high-resolution structural determination techniques. Here, we overcome this issue by separately mutating the Zn(II)-coordinating residues and performing a combination of structural and biochemical analyses on the variant proteins. Structural analyses of Zn(II)-bound AdcAII variants revealed that specific regions within the protein underwent conformational changes via direct coupling to each of the metal-binding residues. Quantitative in vitro metal-binding assays combined with affinity determination and phenotypic growth assays revealed that each of the four Zn(II)-coordinating residues contributes to metal binding by AdcAII. Intriguingly, the phenotypic growth impact of the mutant adcAII alleles was, in general, independent of affinity, suggesting that the Zn(II)-bound conformation of the SBP is crucial for efficacious metal uptake. Collectively, these data highlight the intimate coupling of ligand affinity with protein conformational change in ligand-receptor proteins and provide a putative mechanism for AdcAII. These findings provide further mechanistic insight into the structural and functional diversity of SBPs that is broadly applicable to other prokaryotes.
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spelling pubmed-84168932021-09-05 Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae Župan, Marina L. Luo, Zhenyao Ganio, Katherine Pederick, Victoria G. Neville, Stephanie L. Deplazes, Evelyne Kobe, Boštjan McDevitt, Christopher A. Front Cell Infect Microbiol Cellular and Infection Microbiology Streptococcus pneumoniae scavenges essential zinc ions from the host during colonization and infection. This is achieved by the ATP-binding cassette transporter, AdcCB, and two solute-binding proteins (SBPs), AdcA and AdcAII. It has been established that AdcAII serves a greater role during initial infection, but the molecular details of how the protein selectively acquires Zn(II) remain poorly understood. This can be attributed to the refractory nature of metal-free AdcAII to high-resolution structural determination techniques. Here, we overcome this issue by separately mutating the Zn(II)-coordinating residues and performing a combination of structural and biochemical analyses on the variant proteins. Structural analyses of Zn(II)-bound AdcAII variants revealed that specific regions within the protein underwent conformational changes via direct coupling to each of the metal-binding residues. Quantitative in vitro metal-binding assays combined with affinity determination and phenotypic growth assays revealed that each of the four Zn(II)-coordinating residues contributes to metal binding by AdcAII. Intriguingly, the phenotypic growth impact of the mutant adcAII alleles was, in general, independent of affinity, suggesting that the Zn(II)-bound conformation of the SBP is crucial for efficacious metal uptake. Collectively, these data highlight the intimate coupling of ligand affinity with protein conformational change in ligand-receptor proteins and provide a putative mechanism for AdcAII. These findings provide further mechanistic insight into the structural and functional diversity of SBPs that is broadly applicable to other prokaryotes. Frontiers Media S.A. 2021-08-19 /pmc/articles/PMC8416893/ /pubmed/34490149 http://dx.doi.org/10.3389/fcimb.2021.729981 Text en Copyright © 2021 Župan, Luo, Ganio, Pederick, Neville, Deplazes, Kobe and McDevitt https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Župan, Marina L.
Luo, Zhenyao
Ganio, Katherine
Pederick, Victoria G.
Neville, Stephanie L.
Deplazes, Evelyne
Kobe, Boštjan
McDevitt, Christopher A.
Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae
title Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae
title_full Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae
title_fullStr Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae
title_full_unstemmed Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae
title_short Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae
title_sort conformation of the solute-binding protein adcaii influences zinc uptake in streptococcus pneumoniae
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416893/
https://www.ncbi.nlm.nih.gov/pubmed/34490149
http://dx.doi.org/10.3389/fcimb.2021.729981
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