Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Zupan ML 

PROVIDER: S-EPMC8416893 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

altmetric image

Publications

Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in <i>Streptococcus pneumoniae</i>.

Župan Marina L ML   Luo Zhenyao Z   Ganio Katherine K   Pederick Victoria G VG   Neville Stephanie L SL   Deplazes Evelyne E   Kobe Boštjan B   McDevitt Christopher A CA  

Frontiers in cellular and infection microbiology 20210819


<i>Streptococcus pneumoniae</i> 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-resolut  ...[more]

Similar Datasets

| S-EPMC2911475 | biostudies-literature
| S-EPMC8900738 | biostudies-literature
| S-EPMC3014919 | biostudies-literature
| S-EPMC3928430 | biostudies-literature
| S-EPMC3911161 | biostudies-literature
| S-EPMC8811889 | biostudies-literature
| S-EPMC5655524 | biostudies-literature
| S-EPMC5287374 | biostudies-literature
2011-05-13 | GSE29235 | GEO
| S-EPMC3960169 | biostudies-literature