8Y6F

The crystal structure of MMPs cleavable human heavy chain ferritin

Summary for 8Y6F

• Entry DOI: 10.2210/pdb8y6f/pdb
• Descriptor: Ferritin, CHLORIDE ION, FE (III) ION, ... (5 entities in total)
• Functional Keywords: heavy chain ferritin, mmps cleavable, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 273693.89

Authors

Yuan, C.,Huang, M. (deposition date: 2024-02-02, release date: 2024-07-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.01 Å)