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

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

重组氯毒素构建细胞靶向的活性纳米颗粒(英文)

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这些纳米颗粒可穿透具有和天然毒素相同受体特异性的培养细胞.这些生物相容且可生物降解的材料,表现出与同时作为载体和治疗剂的重组毒素相应的温和但仍然显著的细胞毒活性,有希望成为用于细胞靶向治疗胶质瘤的药物载体.此外,对CTX侧区域的修改可有效影响纳米颗粒的性能,说明基于CTX的构建体可通过常规基因工程来调节其多重功能性.