7EAR

A positively charged mutant Cry3Aa endotoxin

7EAR の概要

• エントリーDOI: 10.2210/pdb7ear/pdb
• 分子名称: Crystaline entomocidal protoxin (2 entities in total)
• 機能のキーワード: crystal-forming, protein delivery, cell-permeable, endosome-escapable, toxin
• 由来する生物種: Bacillus thuringiensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 73292.98

構造登録者

Yang, Z.,Lee, M.M.,Chan, M.K. (登録日: 2021-03-08, 公開日: 2021-04-28, 最終更新日: 2023-11-29)

主引用文献

Yang, Z.,Lee, M.M.M.,Chan, M.K.
Efficient intracellular delivery of p53 protein by engineered protein crystals restores tumor suppressing function in vivo.
Biomaterials, 271:120759-120759, 2021

PubMed Abstract: Direct delivery of proteins into cells holds significant potential for basic research and drug development. However, the poor endosomal escape of conventional delivery strategies remains a challenge, thus limiting the clinical translation of many protein therapeutics. Herein, we report that engineered Cry3Aa protein (Pos3Aa) crystals formed naturally within Bacillus thuringiensis can serve as a vehicle for efficient cytosolic delivery of bioactive proteins. We showed that Pos3Aa-mediated delivery of tumor suppressor p53 protein, a promising therapeutic candidate found to be inactivated in nearly half of human cancers, resulted in the restoration of p53 function in p53-deficient cancer cells, and thereby sensitized them to 5-fluorouracil chemotherapy as demonstrated in in vitro and in vivo models. Our results validate that Pos3Aa crystals can be a robust and effective platform for the cytosolic delivery of effector proteins, and suggest that efficient uptake and endosomal escape could be critical for efficacious p53 protein-based cancer therapy.

PubMed: 33798968
DOI: 10.1016/j.biomaterials.2021.120759

実験手法

X-RAY DIFFRACTION (2.2 Å)