8GZ8
Cryo-EM structure of Abeta2 fibril polymorph1
Summary for 8GZ8
| Entry DOI | 10.2210/pdb8gz8/pdb |
| EMDB information | 34392 |
| Descriptor | peptide self-assembled antimicrobial fibrils (2 entities in total) |
| Functional Keywords | antimicrobial fibrils, amyloid, antimicrobial protein |
| Biological source | Homo sapiens |
| Total number of polymer chains | 52 |
| Total formula weight | 56333.99 |
| Authors | Xia, W.C.,Zhang, M.M.,Liu, C. (deposition date: 2022-09-26, release date: 2023-09-20, Last modification date: 2024-05-22) |
| Primary citation | Wang, F.,Xia, W.,Zhang, M.,Wu, R.,Song, X.,Hao, Y.,Feng, Y.,Zhang, L.,Li, D.,Kang, W.,Liu, C.,Liu, L. Engineering of antimicrobial peptide fibrils with feedback degradation of bacterial-secreted enzymes. Chem Sci, 14:10914-10924, 2023 Cited by PubMed Abstract: Proteins and peptides can assemble into functional amyloid fibrils with distinct architectures. These amyloid fibrils can fulfil various biological functions in living organisms, and then be degraded. By incorporating an amyloidogenic segment and enzyme-cleavage segment together, we designed a peptide (enzyme-cleavage amyloid peptides (EAP))-based functional fibril which could be degraded specifically by gelatinase. To gain molecular insights into the assembly and degradation of EAP fibrils, we determined the atomic structure of the EAP fibril using cryo-electron microscopy. The amyloidogenic segment of EAP adopted a β-strand conformation and mediated EAP-fibril formation mainly steric zipper-like interactions. The enzyme-cleavage segment was partially involved in self-assembly, but also exhibited high flexibility in the fibril structure, with accessibility to gelatinase binding and degradation. Moreover, we applied the EAP fibril as a tunable scaffold for developing degradable self-assembled antimicrobial fibrils (SANs) by integrating melittin and EAP together. SANs exhibited superior activity for killing bacteria, and significantly improved the stability and biocompatibility of melittin. SANs were eliminated automatically by the gelatinase secreted from targeted bacteria. Our work provides a new strategy for rational design of functional fibrils with a feedback regulatory loop for optimizing the biocompatibility and biosafety of designed fibrils. Our work may aid further developments of "smart" peptide-based biomaterials for biomedical applications. PubMed: 37829030DOI: 10.1039/d3sc01089a PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.35 Å) |
Structure validation
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