8Y6F

The crystal structure of MMPs cleavable human heavy chain ferritin

8Y6F の概要

• エントリーDOI: 10.2210/pdb8y6f/pdb
• 分子名称: Ferritin, CHLORIDE ION, FE (III) ION, ... (5 entities in total)
• 機能のキーワード: heavy chain ferritin, mmps cleavable, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 273693.89

構造登録者

Yuan, C.,Huang, M. (登録日: 2024-02-02, 公開日: 2024-07-17)

主引用文献

Yan, W.,Li, H.,Ning, J.,Huang, S.,Jiang, L.,Xu, P.,Huang, M.,Yuan, C.
Engineered protein cages with enhanced extracellular drug release for elevated antitumor efficacy.
Int.J.Biol.Macromol., 267:131492-131492, 2024

PubMed Abstract: Human heavy chain ferritin (HFn) protein cage has been explored as a nanocarrier for targeted anticancer drug delivery. Here, we introduced a matrix metalloproteinases (MMPs)-cleavable sequence into the DE loop of HFn, creating an MMP-responsive variant, MR-HFn, for localized and extracellular drug release. The crystal structure of MR-HFn revealed that the addition of the MMPs recognition sequence did not affect the self-assembly of HFn but presented a surface-exposed loop susceptible to MMPs cleavage. Biochemical analysis indicated that this engineered protein cage is responsive to MMPs, enabling the targeted release of encapsulated drugs. To evaluate the therapeutic potential of this engineered protein cage, monosubstituted β-carboxy phthalocyanine zinc (CPZ), a type of photosensitizer, was loaded inside this protein cage. The prepared CPZ@MR-HFn showed higher uptake and stronger phototoxicity in MMPs overexpressed tumor cells, as well as enhanced penetration into multicellular tumor spheroids compared with its counterpart CPZ@HFn in vitro. In vivo, CPZ@MR-HFn displayed a higher tumor inhibitory rate than CPZ@HFn under illumination. These results indicated that MR-HFn is a promising nanocarrier for anticancer drug delivery and the MMP-responsive strategy here can also be adapted for other stimuli.

PubMed: 38604418
DOI: 10.1016/j.ijbiomac.2024.131492

実験手法

X-RAY DIFFRACTION (2.01 Å)