The spectrum of building block conformers sustains the biophysical properties of clinically-oriented self-assembling protein nanoparticles

Abstract Histidine-rich peptides confer self-assembling properties to recombinant proteins through the supramolecular coordination with divalent cations. This fact allows cost-effective, large-scale generation of microscopic and macroscopic protein materials intriguing biomedical properties. Among such materials, resulting from simple bioproduction building blocks, homomeric nanoparticles are special value as multivalent interactors drug carriers. Interestingly, we have here identified that assembly a given His-tagged might render distinguishable categories nanoparticles. has been scrutinized nanobody-containing fusion EM1-GFP-H6 A3C8-GFP-H6, whose biosynthesis results in two populations blocks. In one them, assembling disassembling is controllable by However, second population immediately self-assembles upon purification non-regulatable pathway, rendering larger specific biological The structural analyses both model revealed important conformational variability renders different functional final soft participation energetically unstable intermediates oligomerization process. These data illustrate complexity Hismediated but they also offer clues for better design refinement protein-based nanomedicines, which, fabrication, show an architectonic flexibility unusual among biomaterials.