Protein P47
Recent research has uncovered a hidden role of the protein p47 in protecting other proteins from mechanical stress inside cells. This discovery could lead to new treatments for diseases where protein stability under force is impaired. Scientists at the S. N. Bose National Centre for Basic Sciences (SNBNCBS) demonstrated that p47 acts as a mechanical chaperone, stabilising proteins under physical strain. This challenges previous views that p47 was only an accessory helper to the cellular machine p97. The findings open new avenues in understanding cellular mechanics and protein quality control.
Role of Mechanical Stress in Cells
Proteins inside cells constantly face mechanical forces. These arise during vital processes like transport, degradation, and cytoskeletal changes. Such forces can cause proteins to unfold or misfold, affecting their function. Cellular health depends on proteins maintaining their shape despite these stresses. Until now, canonical chaperones were known to assist protein folding. Whether accessory proteins could directly protect proteins under force was unclear.
Discovery of p47’s Mechanical Chaperone Activity
The study led by Dr Shubhasis Haldar used single-molecule magnetic tweezers to apply controlled forces on proteins. This mimicked the physical strains proteins encounter in living cells. The experiments showed that p47 binds to proteins under mechanical stretch and helps them refold. This foldase-like activity was unexpected for a cofactor previously seen only as an assistant to p97. P47’s ability to stabilise proteins under force marks it as a mechanical chaperone.
Functions of p47 and p97 in Cells
P97 is a powerful cellular machine involved in protein movement and degradation. P47 is its cofactor, traditionally known for roles in protein trafficking, membrane fusion, and degradation. The new findings reveal that p47 also enhances the mechanical efficiency of extracting proteins from the endoplasmic reticulum (ER) lumen into the cytoplasm. It helps polypeptides pass through narrow pores while reducing the risk of misfolding.
Implications for Disease and Therapeutics
Many diseases arise from proteins becoming unstable under mechanical forces. These include heart muscle diseases and genetic disorders called laminopathies. Targeting mechanical cofactors like p47 could offer new therapeutic strategies. By boosting protein stability under force, treatments may prevent cellular damage and improve disease outcomes. This expands the known functional repertoire of accessory proteins beyond their classic roles.
Significance of Single-Molecule Evidence
The study provides the first direct, single-molecule proof that cofactors can have autonomous, force-dependent protective functions. This challenges the traditional view that only canonical chaperones assist protein folding under stress. It suggests a broader role for accessory proteins in cellular mechanics and protein quality control. Such insights may prompt further research into mechanical chaperones and their biomedical potential.
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