According to recent reports by the S. N. Bose National Centre of Basic Sciences (SNBNCBS) , however, the protein p47 has a startling new role--that of a mechanical chaperone which shields other proteins against physical stress within cells. So far, p47 was only regarded as an auxiliary to the cellular machine p97 , and the results indicate that it has a separate role in protein stability in presence of force. The finding may be the basis of new therapeutic approaches to diseases associated with protein misfolding and instability.
Stress of the mechanics and the stability of proteins.
Within living cells, proteins are constantly exposed to mechanical forces that are created and exerted in very important processes such as transport, folding, degradation and reorganization of the cytoskeleton. The forces may result in unfolding or misfolding of proteins and consequently dysfunction and cellular stress. Canonical chaperons have traditionally been considered as the only proteins safeguards when such conditions arise. It was yet unknown whether accessory proteins would have the same functions.
p47 Discovery of Protective Role.
Single-molecule magnetic tweezers were applied to investigate the properties of proteins under mechanical strain when exposed to a particular configuration (drain-free setup). The group that conducted the study, led by Dr. Shubhasis Haldar , simulated the mechanical strain to which proteins are subjected to under real cellular conditions. These experiments revealed that p47 is able to bind to unfolded proteins and that they can be actively refolded by it, indicating the foldase-like activity . This came as a surprise, with p47 having been only known to aid p97. The results re-characterize p47 as a force-stabilizing mechanical chaperone of proteins.
Relationship Between p47 and p97
Protein p97 is an essential cellular motor that aids in the transportation and degradation of proteins, particularly in such processes as endoplasmic reticulum (ER)-associated degradation . Its cofactor P47 was regarded to have a role in protein trafficking, membrane fusion and degradation . The new research shows that p47 does not only support p97, but also increases the mechanical efficiency of ER protein extraction. It provides a better diffusion of polypeptides through fine pores and decreases the probability of misfolding.
Therapeutic Implications
Stability of proteins under force is associated with diseases like the cardiomyopathies and laminopathies . The p47 mechanical stabilizer provides promising treatment opportunities. The increase in the activity of p47 or other cofactors may help avoid damage to proteins, decrease cellular stress, and offer new treatment options to mechanical force-related diseases.
Broader Significance
The paper represents the first direct single-molecule demonstration that proteins can be safeguarded by accessory proteins such as p47 that may function independently of other proteins in mechanical stress response. It questions the traditional assumption that canonical chaperones are the only ones responsible to do this job. The finding expands the concept of cellular mechanics and protein quality management and provides new avenues of biomedical studies and therapeutic development.
Conclusion
Mechanical chaperone of p47 is a paradigm shift in cell biology .
Month: Current Affairs - September 08, 2025
Category: current affairs daily