Impact of Changes in Buffer Ionic Concentration and Mutations on a GH1 β‑Glucosidase Homodimer

缓冲液离子浓度变化和突变对 GH1 β-葡萄糖苷酶同源二聚体的影响

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Abstract

Oligomerization is a key feature of protein function, with approximately 30% of proteins exhibiting this trait. The homodimeric form of proteins, such as the GH1 β-glucosidase from Spodoptera frugiperda (Sfβgly), plays a significant role in enzyme activity. In this study, we investigate the homodimerization of Sfβgly, which forms a cyclic C2 dimer with a well-defined interface. Using size exclusion chromatography and SEC-MALS, we characterized the homodimerization behavior of Sfβgly at equilibrium conditions in different ionic concentrations of phosphate buffer. The dissociation constants (K (D)) increase with decreasing ionic concentration, suggesting that the hydrophobic effect is central to homodimer formation. Site-directed mutagenesis of key residues at the dimer interface further elucidated the contributions of specific amino acid residues to dimer stability. Mutations affecting both, apolar and hydrogen bond-forming residues, significantly increased the K (D). However, mutations of hydrogen bond-forming residues caused a smaller K (D) change than apolar residue mutations, suggesting that while the latter is the driving factor in the dimerization, the former could play a role in guiding the monomers relative orientation. These findings enhance our understanding of protein oligomerization in GH1 β-glucosidases and its implications for protein design and function.

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