Researchers at UCLA, the California NanoSystems Institute, the David Geffen School of Medicine, and the Howard Hughes Medical Institute have modeled the structure of the largest cellular structure ever crystallized, suggesting ways to engineer the particles for drug delivery. The study focuses on newly engineered nanomaterial vaults for use as a drug therapy vehicle.
Vaults are large barrel-shaped particles that are found in the cytoplasm of all mammalian cells, which may function in innate immunity. As naturally-occurring nano-scale capsules, vaults may be useful objects to engineer as therapeutic delivery vehicles. For the study, the team of researchers proposed an atomic structure for the thin outer shell of the vault.
“Our draft model is essentially an atomic-level vault with a completely unique structure—like a barrel with staves—it is unlike any other large structure found in nature,” said Leonard H. Rome. “The outside of the vault structure is like an eggshell; a continuous protective barrier with no gaps.”
The shell is made up of 96 identical protein chains, each of 873 amino acid residues, folded into 14 domains. Each chain forms an elongated stave of half the vault, as well as the cap of the barrel-like shell.
“These nano-structured vaults offer a human-friendly nano-container, like a molecular level C5A transport jet, with a cargo hold large enough to encompass a whole ribosome with their hundreds of proteins and nucleic acids, or enough drugs to control a cell,” said David Eisenberg.
The construction of the draft atomic model lays the foundation for further studies of vaults and will guide projects of vault engineering with the intention towards targeted release of vault contents for drug delivery.
Citation: Anderson DH, Kickhoefer VA, Sievers SA, Rome LH, Eisenberg D (2007) Draft crystal structure of the vault shell at 9-A° resolution. PLoS Biol 5(11): e318. doi:10.1371/journal.pbio.0050318