Hyderabad: Researchers at the Centre for DNA Fingerprinting and Diagnostics (CDFD) have achieved a breakthrough in cellular signalling.
Dr Rashna Bhandari's group, in collaboration with a team of researchers from Germany, has identified a new protein modification, pyrophosphorylation, that can ultimately influence cellular functions impacting blood sugar regulation, body weight control, and male fertility. The findings, conducted in partnership with Dr Dorothea Fiedler were published in Nature Chemical Biology.
Speaking to Deccan Chronicle, Dr Bhandari elaborated on her research: “There are different types of sugars produced in the body, one of which is inositol, which can accumulate phosphate groups. We discovered that a specific form of this sugar, called InsP7 (inositol pyrophosphate), can transfer a phosphate group to proteins, altering their functions. This process is part of cell signalling, where cells communicate and coordinate actions within the body.”
Dr Fiedler’s chemical biology lab identified 71 proteins carrying this unique modification, and Dr Bhandari and her team showed that InsP7 is responsible for this phenomenon.
“InsP7 modifies proteins by adding a second phosphate, creating a diphosphate or pyrophosphate group. Pyrophosphate carries more energy than a single phosphate, which is why it’s referred to as ‘pyro,’ implying high energy. Dr Fiedler’s team developed a method to detect these diphosphate modifications on proteins, and our research has found that this specific modification affects many cell functions" she explained.
Furthermore, the study revealed that many proteins undergoing this modification are involved in ribosome formation, which is crucial for protein synthesis in cells. Reduced InsP7 levels impair this process, affecting protein production and, consequently, various cellular functions.
Dr Bhandari's research has shown that InsP7 plays a critical role in multiple bodily functions, such as blood clotting, body weight, and male fertility. For example, mice with lower InsP7 levels exhibit disruptions in these areas.
This study marks a significant advancement at the molecular level in detecting protein pyrophosphorylation, a previously underexplored modification due to technical limitations.
"Dr Fiedler’s method now allows us to detect not just a few but dozens of proteins with this modification. This breakthrough enables us to investigate the broader impact of these modifications on cellular and organismal functions, providing valuable insights into how they may maintain normal cellular activity,” said Dr Bhandari.
This discovery opens new avenues for exploring additional cellular functions impacted by protein pyrophosphorylation, offering potential insights for future studies.
