Conversion of the Native 24-mer Ferritin Nanocage into Its Non-Native 16-mer Analogue by Insertion of Extra Amino Acid Residues
Shengli Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorJiachen Zang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorWenming Wang
Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006 China
Search for more papers by this authorHai Chen
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorXiaorong Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorFudi Wang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorCorresponding Author
Prof. Hongfei Wang
Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006 China
Search for more papers by this authorCorresponding Author
Prof. Guanghua Zhao
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorShengli Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorJiachen Zang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorWenming Wang
Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006 China
Search for more papers by this authorHai Chen
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorXiaorong Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorFudi Wang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorCorresponding Author
Prof. Hongfei Wang
Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006 China
Search for more papers by this authorCorresponding Author
Prof. Guanghua Zhao
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083 China
Search for more papers by this authorGraphical Abstract
Shaping proteins: The ferritin cage exhibits high selectivity and has been utilized as a delivery vehicle for anticancer drugs or imaging agents. However, its assembly has been limited to a single size and shape. By tuning the interfacial interaction of recombinant human H-chain ferritin (rHuHF) subunits through amino acid residues insertion, a novel, lower symmetrical ferritin-like nanocage was produced and crystallographically investigated.
Abstract
Protein assemblies with high symmetry are widely distributed in nature. Most efforts so far have focused on repurposing these protein assemblies, a strategy that is ultimately limited by the structures available. To overcome this limitation, methods for fabricating novel self-assembling proteins have received intensive interest. Herein, by reengineering the key subunit interfaces of native 24-mer protein cage with octahedral symmetry through amino acid residues insertion, we fabricated a 16-mer lenticular nanocage whose structure is unique among all known protein cages. This newly non-native protein can be used for encapsulation of bioactive compounds and exhibits high uptake efficiency by cancer cells. More importantly, the above strategy could be applied to other naturally occurring protein assemblies with high symmetry, leading to the generation of new proteins with unexplored functions.
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