S100 proteins are a family of calcium-binding proteins involved in a wide range of physiological and pathological processes. While substantial structural and functional information exists for S100 homodimers, the heterodimerization of S100 proteins remains poorly studied, and its biological significance is largely unknown. In particular, the influence of heterodimerization on membrane-binding properties and their modulation by calcium has yet to be fully elucidated. In this study, the calcium-dependent and independent membrane-binding behavior of S100A1, S100B, S100P, and their heterodimers (S100A1-S100B and S100A1-S100P) was investigating using a Langmuir monolayer model combined with surface tensiometry to probe protein-lipid interactions under controlled environments. The proteins were overexpressed in Escherichia coli and purified via affinity and hydrophobic interaction chromatographies. Binding parameters of the purified proteins and their heterodimers were evaluated in the presence and absence of calcium ions. Surface pressure analyses revealed distinct binding profiles, modulated by calcium. S100B exhibited enhanced membrane interaction upon calcium binding, while S100A1 and its heterodimers displayed reduced membrane association in the calcium-bound state. Interestingly, S100P showed calcium-independent behavior, whereas the S100A1-S100P heterodimer demonstrated unique lipid-binding properties, suggesting that heterodimerization significantly influences membrane interaction. These findings provide valuable insights into the interplay between calcium signaling, dimerization, and phospholipid interactions in the S100 protein family. They also highlight the structural and functional diversity within the S100 family and emphasize the potential role of heterodimerization in modulating protein-membrane interactions.
Jaouen et al. (Wed,) studied this question.