Work

Affibodies as valuable tool to prevent β2m aggregation under lysosomal-like conditions

Year: 2025

Type: article

Abstract: Beta-2 microglobulin (β 2 m) is a small protein that forms the invariant subunit of the Major Histocompatibility Complex I. Monomeric β 2 m is stable under physiological conditions, however high local concentrations can induce misfolding, leading to amyloid deposition. This accumulation has been recently observed in the lysosomes of tumour-associated macrophages from patients affected by multiple myeloma. Such aggregation has been linked to inflammation and tumour progression. Stabilizing the native state of β 2 m could be the first step towards preventing this cancer-promoting process. To achieve this goal, the effect of affibody molecules, small and stress-resistant affinity proteins, was tested. Three affibodies molecules were selected against β 2 m. Affibody-β 2 m complex formation was initially assessed by size exclusion chromatography and subsequently confirmed by microscale thermophoresis and isothermal titration calorimetry. In parallel, in presence of one of the affibody (Z β2m_01 ) a significant reduction in β 2 m aggregation was observed. The inhibition of amyloid formation was also confirmed by transmission electron microscopy. Taken together, these results indicate that Z β2m_01 has the potential to act as β 2 m aggregation inhibitor under lysosomal-like pH values.

Source: Biology Direct

DOI: 10.1186/s13062-025-00659-2