Structure of bacterial protection
Physicists have studied the structure that protects the genome of bacteria from antibiotics
Russian physicists have investigated the structure of a crystalline DNA complex with a stress-induced Dps protein. It is the main factor in protecting the DNA-containing area of the cell from adverse conditions, including the action of antibiotics. During the study, scientists for the first time managed to examine in detail the Dps-DNA crystal complex and determine its parameters using the method of small-angle X-ray scattering and cryo-electron tomography. In the future, the knowledge gained by the researchers will help overcome the problem of bacterial resistance to antibiotics and allow the development of new pharmaceuticals.
The scientists reported on their work in the journal FEBS Letters (Dadinova et al., Protective Dps–DNA co‐crystallization in stressed cells: an in vitro structural study by small‐angle X‐ray scattering and cryo‐electron tomography). The research is supported by a grant from the Presidential Research Projects Program of the Russian Science Foundation (RNF).
Many bacteria, in response to stressful conditions such as oxidative stress, heat shock, exposure to ultraviolet radiation, radiation and antibiotics, form highly ordered, non-volatile intracellular structures that well protect the DNA of the bacterial cell. This strategy was first identified in E. coli in 1992. The defense mechanism consists in the joint crystallization of the cell's DNA with the Dps protein, the active production of which in the cell occurs just under stressful conditions. Despite numerous subsequent studies of this mechanism, no one has been able to fully visualize the complex in detail and determine the position of DNA in the crystal structure. Scientists faced a difficult task to determine the structure of this complex for further research.
"To visualize and determine the parameters of the structure of the Dps-DNA complex, we used two complementary structural methods: small-angle X-ray scattering and cryo-electron tomography. The first method allowed rapid screening of conditions for protein and DNA co-crystallization, as well as determining the parameters of the crystal lattice with a high degree of accuracy. With the help of the second one, for the first time we were able to observe the mutual arrangement of Dps and DNA molecules in the complex.
As far as we know, these methods and approaches have never been used before to study Dps-DNA crystals. Thus, we have determined the conditions for the formation of complexes, their parameters, size and type of packaging," says Lyubov Dadinova, PhD in Physics and Mathematics, researcher at the Federal Research Center "Crystallography and Photonics" of the Russian Academy of Sciences (Moscow), project manager for the RNF grant.
By combining data obtained using small-angle X-ray scattering and cryo-electron tomography, scientists were able to visualize the Dps-DNA complex and uniquely determine the position of protein and DNA in the complex. Physicists have learned that co-crystals have a crystal structure of three vectors, have sizes from 80 to 300 nm and consist of 3-8 layers formed by Dps alternating with layers of parallel or antiparallel stacked DNA chains, probably partially wrapping the protein.
The work of Russian scientists in the field of research of Dps-DNA complexes will have a great impact on the world pharmacy. Elucidation of the fundamental biochemical, genetic and structural foundations of micrograinism resistance to negative factors is of paramount importance for the development of innovative therapeutic approaches.
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