Researchers at the Indian Institute of Science (IISc), with collaborators from the Institute of Mathematical Sciences (IMSc), have discovered how a key protein in the tuberculosis bacterium helps protect it from the influence of foreign DNA inserted into its genome.
The IISc said that understanding how this protein, called Lsr2, functions could help develop drugs that target it, thereby aiding in the fight against TB.
“This protein is interesting to study as it controls a large set of genes in the bacteria,” said Mahipal Ganji, assistant professor at the Department of Biochemistry, IISc, and corresponding author of the study.
The scientists have earlier shown that Lsr2 is crucial for Mycobacterium tuberculosis (Mtb) to infect other organisms.
In the current study, the team found that this protein silences regions of Mtb DNA which contain genetic material that foreign organisms such as viruses may have inserted into its genome. When a cell produces proteins encoded by foreign DNA, it may interfere with its own functioning. So, it is crucial for the cell to identify and stop these genes from being expressed.
Proteins typically regulate DNA expression by binding to specific sequences of bases (adenine, guanine, thymine or cytosine) on the genome, and stopping the cell’s machinery from “reading” the DNA in order to produce the protein.
The team found that Lsr2 binds to large regions of the DNA that are rich in the bases adenine (A) and thymine (T). Intriguingly, if there are enough Lsr2 proteins close to each other, they start sticking together. This clumping or condensation prevents the DNA regions from being read and transcribed. This is a unique mechanism that Lsr2 uses to block the production of proteins that may harm the bacteria.
“We never expected the protein to form condensates. We were initially doing single molecule experiments and we saw hints that maybe it was forming these condensates, and then we investigated further,” said Mr. Ganji.
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