7EAR
A positively charged mutant Cry3Aa endotoxin
Summary for 7EAR
| Entry DOI | 10.2210/pdb7ear/pdb |
| Descriptor | Crystaline entomocidal protoxin (2 entities in total) |
| Functional Keywords | crystal-forming, protein delivery, cell-permeable, endosome-escapable, toxin |
| Biological source | Bacillus thuringiensis |
| Total number of polymer chains | 1 |
| Total formula weight | 73292.98 |
| Authors | Yang, Z.,Lee, M.M.,Chan, M.K. (deposition date: 2021-03-08, release date: 2021-04-28, Last modification date: 2023-11-29) |
| Primary citation | 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 Cited by 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: 33798968DOI: 10.1016/j.biomaterials.2021.120759 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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