Dextran sulfate acting as a chaperone-like component on inhibition of amorphous aggregation and enhancing thermal stability of ovotransferrin

•Dextran sulfate (DS) facilitates OVT to form soluble aggregates with higher charge, smaller size, more compact structure, and lower surface hydrophobicity.•The thermal tolerance of OVT against pasteurization was significantly improved by adding DS.•DS exhibited chaperone-like activities by preventing protein aggregation and restoration of OVT structure. The tendency of ovotransferrin (OVT) to unfold and aggregate under 60 °C severely restricted sterilization temperature during egg processing. Searching for efficient strategies to improve OVT thermal stability is essential for improving egg product quality and processing suitability. Here, we investigated the effect of sulfate polysaccharide (dextran sulfate, DS) on heat-induced aggregation of OVT. We found that DS can effectively suppress amorphous aggregation of OVT at pH 7.0 after heating. Strikingly, the addition of 5 µM DS fully suppressed insoluble aggregates formation of 0.5 mg/mL OVT. Structure analysis confirmed that DS preserves nearly the entire secondary and tertiary structure of OVT during heating. The steric hindrance effect arising from strong electrostatic interactions between OVT and DS, coupled with reduced OVT hydrophobicity, is the underlying mechanism in suppressing protein–protein interactions, thus enhancing thermal stability. These findings suggest DS could act as protein stabilizers and chaperones, enhancing the thermostability of heat-sensitive proteins.