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Updated: Jun 23, 2026
Essential Metal Uptake in Gram-negative Bacteria: X-ray Fluorescence, Radioisotopes, and Cell Fractionation
Published on: February 1, 2018
Crystal structure and metal binding properties of the lipoprotein MtsA, responsible for iron transport in
Xuesong Sun1, Heather M Baker, Ruiguang Ge
1Institute of Life and Health Engineering and National Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, PR China.
Abstract:
An ability to acquire iron is essential for the viability and growth of almost all organisms and in pathogenic bacteria is strongly correlated with virulence. The cell surface lipoprotein MtsA, a component of the MtsABC transporter of Streptococcus pyogenes, acts as the primary receptor for inorganic iron by this significant human pathogen. Iron is bound as Fe(2+), with the participation of bicarbonate. The crystal structure of MtsA has been determined and refined at 1.8 A resolution (R = 0.167, and R(free) = 0.194). MtsA has the classic bacterial metal binding receptor (MBR) fold, with the Fe(2+) ion bound to the side chains of His68, His140, Glu206, and Asp281, at a totally enclosed site between the two domains of the protein. The absence of bicarbonate from the binding site suggests that it is displaced during the final stages of metal binding. Both the fold and metal binding site are most similar to those of the manganese receptors PsaA and MntC, consistent with the similar coordination requirements of Fe(2+) and Mn(2+). Binding studies confirm a 10-fold preference for Fe(2+) over Mn(2+), although both may be carried in vivo. Mutational analysis of the binding site shows that His140 is critical for a fully functional binding site but that Glu206 is dispensable. The crystal structure explains the distinct roles of these ligands and also reveals potential secondary binding sites that may explain the binding behavior of MtsA for metal ions other than Fe(2+).
Insights
Pathogenic bacteria like Streptococcus pyogenes use the MtsA protein to acquire essential iron. Researchers determined the crystal structure of MtsA, revealing its iron-binding mechanism and similarities to manganese receptors.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Iron acquisition is crucial for bacterial survival and virulence.
- Streptococcus pyogenes utilizes the MtsABC transporter, with MtsA as the primary inorganic iron receptor.
- Iron is transported as Fe(2+) with bicarbonate involvement.
Purpose of the Study:
- To determine the crystal structure of the MtsA protein from Streptococcus pyogenes.
- To elucidate the mechanism of Fe(2+) binding by MtsA.
- To understand the structural basis for MtsA's specificity and function.
Main Methods:
- X-ray crystallography to determine the MtsA structure at 1.8 Å resolution.
- Protein refinement with R = 0.167 and R(free) = 0.194.
- Mutational analysis and binding studies to investigate ligand roles and metal ion preference.
Main Results:
- MtsA exhibits the classic bacterial metal binding receptor (MBR) fold.
- Fe(2+) is bound within an enclosed site involving His68, His140, Glu206, and Asp281.
- Bicarbonate appears to be displaced during metal binding.
- MtsA shows structural and functional similarity to manganese receptors PsaA and MntC.
- A 10-fold preference for Fe(2+) over Mn(2+) was observed.
- His140 is critical for function, while Glu206 is dispensable.
- Potential secondary binding sites were identified.
Conclusions:
- The crystal structure provides insights into the Fe(2+) binding mechanism of MtsA.
- MtsA's structure explains its preference for Fe(2+) over Mn(2+) and the roles of key residues.
- The findings contribute to understanding iron acquisition strategies in pathogenic bacteria.
- Structural data can inform the development of novel antimicrobial strategies targeting iron uptake.
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