Scientists decode molecular traps, viral infections to arrest infections

Scientists at the Hyderabad-based CSIR-CCMB have successfully decoded ‘sticky molecular traps used by plants to arrest viral infections.
 
Plants are known to use liquid-like, sticky protein droplets to trap and disable attacking viruses. The researchers at the CSIR-Centre for Cellular and Molecular Biology (CCMB)
have revealed this key defense system in plants. 
 
The study led by Dr Mandar V. Deshmukh has been published in the Journal of the American Chemical Society (JACS). The paper provides a molecular-level mechanism to explain this
process.
 
Many viruses contain double-stranded RNA (ribonucleic acid) as their genetic material. Plants make certain proteins more when they are infected by viruses, which can identify the viral RNAs. They are called RNA-binding proteins. 

Some of these proteins can bind to the virus’s genetic machinery at positions called the Viral Replication Complexes, and stall the genetic machinery from dividing. Unable to divide its genetic material, a virus fails to replicate itself in infected cells. 

Practical applications

“Understanding these states and the mechanism has significant implications for both basic science as well as translations in agricultural and medical biotechnology,” said Dr Deshmukh.
 
For agriculture, this discovery opens new avenues for developing crop varieties with enhanced natural immunity. By mimicking or strengthening these protein-based traps, scientists can design plants that are more resilient to devastating viral outbreaks that cause billions of dollars in crop losses globally. 
 
In human cells, the study opens up the possibility for scientists to manipulate these sticky protein patches, to dissolve neurotoxic clumps associated with dementia or dismantle liquid barriers that protect growing tumours.
 
Moreover, a thorough understanding of these molecular mechanisms would allow scientists to design drugs that precisely manipulate the sticky protein patches, the study pointed out. 
 
However, the details of the proteins binding to the RNA remained a mystery for a long time.
 
Traditionally, RNA-binding proteins have been assumed to latch onto double-stranded RNA, as a key fits into a lock.

New research findings

Using advanced techniques such as Nuclear Magnetic Resonance (NMR) spectroscopy, fluorescence microscopy, and molecular dynamics simulations, the CCMB group found more to these lock and key structures. 
 
According to the research paper, they discovered a unique fold in double-stranded RNA-binding proteins. In this fold, electric charges are distributed on the surface of the proteins such that they create sticky patches.
 
Positive electric charges attract negative charges. These charges are distributed across the proteins, attracting and binding them to one another. This interconnected mesh of proteins forms “…Act like a molecular glue”, says Dr Jaydeep Paul, first author of the study.
 
“By forming these dense, gel-like droplets, the plant cells effectively trap the viral RNA, preventing it from interacting with the machinery needed for replication”, explains Dr Paul.
These droplets, also known as biomolecular condensates, represent a shift in how scientists understand a living cell.

“Rather than a collection of static membrane-bound compartments like the nucleus and mitochondria, the cell is now seen as a dynamic environment in which membrane-less organelles form like oil droplets in water.