7LM5

Crystal structure of the Zn(II)-bound AdcAII H65A mutant variant of Streptococcus pneumoniae

Summary for 7LM5

• Entry DOI: 10.2210/pdb7lm5/pdb
• Descriptor: Adhesion protein, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: sbp, atp-binding cassette transporter, zn acquisition, metal binding protein
• Biological source: Streptococcus pseudopneumoniae 5247
• Total number of polymer chains: 1
• Total formula weight: 33464.01

Authors

Luo, Z.,Zupan, M.,McDevitt, C.A.,Kobe, B. (deposition date: 2021-02-05, release date: 2021-09-29, Last modification date: 2023-10-18)

Primary citation

Zupan, M.L.,Luo, Z.,Ganio, K.,Pederick, V.G.,Neville, S.L.,Deplazes, E.,Kobe, B.,McDevitt, C.A.
Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae .
Front Cell Infect Microbiol, 11:729981-729981, 2021

PubMed Abstract: 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 direct coupling to each of the metal-binding residues. Quantitative 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 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.

PubMed: 34490149
DOI: 10.3389/fcimb.2021.729981

Experimental method

X-RAY DIFFRACTION (2.4 Å)