METAL BINDING PROTEIN / Nano-delivery platform / De novo Design / Ferritin / Rabies virus Glycoprotein domain III (RABV-GDIII) / GDIII-Ferritin Nano-vaccine / stabilized / Strong immune response
機能・相同性
機能・相同性情報
iron ion sequestering activity / ferritin complex / negative regulation of ferroptosis / Scavenging by Class A Receptors / Golgi Associated Vesicle Biogenesis / ferroxidase / autolysosome / ferroxidase activity / negative regulation of fibroblast proliferation / ferric iron binding ...iron ion sequestering activity / ferritin complex / negative regulation of ferroptosis / Scavenging by Class A Receptors / Golgi Associated Vesicle Biogenesis / ferroxidase / autolysosome / ferroxidase activity / negative regulation of fibroblast proliferation / ferric iron binding / autophagosome / Iron uptake and transport / ferrous iron binding / tertiary granule lumen / iron ion transport / ficolin-1-rich granule lumen / intracellular iron ion homeostasis / immune response / iron ion binding / negative regulation of cell population proliferation / Neutrophil degranulation / extracellular exosome / extracellular region / identical protein binding / nucleus / membrane / cytosol / cytoplasm 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2024 タイトル: Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate. 著者: Dan Fu / Wenming Wang / Yan Zhang / Fan Zhang / Pinyi Yang / Chun Yang / Yufei Tian / Renqi Yao / Jingwu Jian / Zixian Sun / Nan Zhang / Zhiyu Ni / Zihe Rao / Lei Zhao / Yu Guo / 要旨: Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates ...Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (G) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases.
A: Native peptide,Ferritin heavy chain B: Native peptide,Ferritin heavy chain C: Native peptide,Ferritin heavy chain D: Native peptide,Ferritin heavy chain E: Native peptide,Ferritin heavy chain F: Native peptide,Ferritin heavy chain G: Native peptide,Ferritin heavy chain H: Native peptide,Ferritin heavy chain I: Native peptide,Ferritin heavy chain J: Native peptide,Ferritin heavy chain K: Native peptide,Ferritin heavy chain L: Native peptide,Ferritin heavy chain M: Native peptide,Ferritin heavy chain N: Native peptide,Ferritin heavy chain O: Native peptide,Ferritin heavy chain P: Native peptide,Ferritin heavy chain Q: Native peptide,Ferritin heavy chain R: Native peptide,Ferritin heavy chain S: Native peptide,Ferritin heavy chain T: Native peptide,Ferritin heavy chain U: Native peptide,Ferritin heavy chain V: Native peptide,Ferritin heavy chain W: Native peptide,Ferritin heavy chain X: Native peptide,Ferritin heavy chain
名称: Macromolecule:FTH1 ligand:Peptide / タイプ: COMPLEX 詳細: The overall structure of the complex can be described as consisting of self-assembled human ferritin 24-mer and 24 peptides. Entity ID: all / 由来: RECOMBINANT
分子量
値: 2.3 kDa/nm / 実験値: YES
由来(天然)
生物種: Homo sapiens (ヒト)
由来(組換発現)
生物種: Colibacter (バクテリア)
緩衝液
pH: 8 / 詳細: 250mM NaCl, 50mM Tris-HCL, pH 8.0
緩衝液成分
ID
濃度
名称
式
Buffer-ID
1
250mM/L
sodiumchloride
NaCl
1
2
50mM/L
Trishydroxymethylaminomethane
Tris
1
試料
濃度: 1.6 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES
試料支持
グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in.
急速凍結
装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K