Conformation of the solute-binding protein AdcAII influences zinc uptake in streptococcus pneumoniae

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dc.contributor.authorŽupan, M.L.
dc.contributor.authorLuo, Z.
dc.contributor.authorGanio, K.
dc.contributor.authorPederick, V.G.
dc.contributor.authorNeville, S.L.
dc.contributor.authorDeplazes, E.
dc.contributor.authorKobe, B.
dc.contributor.authorMcDevitt, C.A.
dc.date.issued2021
dc.description.abstractStreptococcus 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.
dc.description.statementofresponsibilityMarina L. Župan, Zhenyao Luo, Katherine Ganio, Victoria G. Pederick, Stephanie L. Neville, Evelyne Deplazes ... et al.
dc.identifier.citationFrontiers in Cellular and Infection Microbiology, 2021; 11:729981-1-729981-15
dc.identifier.doi10.3389/fcimb.2021.729981
dc.identifier.issn2235-2988
dc.identifier.issn2235-2988
dc.identifier.orcidMcDevitt, C.A. [0000-0003-1596-4841]
dc.identifier.urihttps://hdl.handle.net/2440/132463
dc.language.isoen
dc.publisherFrontiers Media SA
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1180826
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1071659
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1142695
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1122582
dc.relation.granthttp://purl.org/au-research/grants/arc/LE170100200
dc.relation.granthttp://purl.org/au-research/grants/arc/DP170102102
dc.relation.granthttp://purl.org/au-research/grants/arc/FL180100109
dc.relation.granthttp://purl.org/au-research/grants/arc/FT170100006
dc.rights© 2021 Ž upan, Luo, Ganio, Pederick, Neville, Deplazes, Kobe and McDevitt. 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.
dc.source.urihttps://doi.org/10.3389/fcimb.2021.729981
dc.subjectStreptococcus pneumoniae; zinc; solute-binding protein; ABC transporter; host-pathogen
dc.titleConformation of the solute-binding protein AdcAII influences zinc uptake in streptococcus pneumoniae
dc.typeJournal article
pubs.publication-statusPublished

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