Bioconjugation of gold nanoclusters to lysozyme increases resistance to amyloid formation via stabilization of a β-sheet intermediate

Bioconjugation of gold nanoclusters (AuNC) onto protein scaffolds is a popular technique in the bioengineering field due to its broad applications in modulating protein structure and function. Recent work showed that AuNC bioconjugation could alter the structure of hen egg white lysozyme (Lys), converting the normally α-helical protein into a predominantly β-sheet structure with reduced antibody binding. Unfunctionalized Lys is often used as a model for amyloid fibril formation. Here, Lys undergoes a similar α-helix to β-sheet transition, the end product of which aggregates to form insoluble amyloid fibrils. Despite these similarities, our work shows that the β-sheet AuNC-Lys bioconjugate is highly resistant to fibril formation under a range of amylogenic conditions and could even inhibit amyloid formation in native, unfunctionalized Lys. These results illustrate the potential of AuNC bioconjugation to “trap” amylogenic proteins in their partially unfolded intermediate state without triggering further fibril formation. This could have implications for the future design and use of AuNC-based biomolecules while opening up new avenues for therapeutic design.