21LE
Crystal strucrue of HuHF-C2-CAR complex
Summary for 21LE
| Entry DOI | 10.2210/pdb21le/pdb |
| Descriptor | Ferritin heavy chain, N-terminally processed, MAGNESIUM ION, CARMUSTINE, ... (5 entities in total) |
| Functional Keywords | huhf, dacarbazine, complex, protein design, metal binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 20370.13 |
| Authors | |
| Primary citation | Wang, W.,Yao, H.,Gong, W.,Ma, D.,Qiao, J.,Zhang, Y.,Wu, L.,Fan, C.,Zhao, Y.,Wang, Z.,Jia, Z.,Guo, Y.,Zhang, N.,Zhao, G.,Yun, Y.,Wang, H. Redesign of the Ferritin Ferroxidase Center for Universal Molecular Binding or Specific Recognition. Small, :e73922-e73922, 2026 Cited by PubMed Abstract: Although ferritin, as a versatile nanocarrier, has been engineered to improve cargo loading efficiency for various functions, including therapeutic applications, a universal design strategy enabling tunable molecular binding remains an unmet challenge. This study reports an AI-aided structure-guided engineering approach targeting the ferroxidase center of recombinant human heavy-chain ferritin (rHuHF), aiming to achieve either universal molecular binding or high-affinity specific recognition. Through site-directed mutagenesis of key residues within and flanking the ferroxidase center, two rHuHF variants (rHuHF-C1 and rHuHF-C2) were generated. X-ray crystallographic analysis revealed that the engineered pocket within rHuHF-C2 can accommodate a broad range of hydrophobic molecules (e.g., Curcumin, CUR) via hydrophobic interactions, thus validating their universal molecular binding capability. On the other hand, leveraging AI-assisted rational design, a variant (rHuHF-71) was subsequently engineered to specifically bind CUR with enhanced affinity, facilitated by the formation of hydrogen bonds and optimized hydrophobic contacts. This work establishes a generalizable strategy, designated as "Excavation, Rebuilding, and Validation", for engineering ferritin nanocages with tunable binding specificities, which holds great promise for advancing the development of protein-based drug delivery systems and the design of small-molecule binding proteins. PubMed: 42178779DOI: 10.1002/smll.73922 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
Download full validation report
