Researchers report that they have modeled the structure of a vault, large barrel-shaped particles that are found in the cytoplasm of all mammalian cells. As naturally occurring nanoscale capsules, they believe that vaults may be useful as therapeutic delivery vehicles. The new model provides insight on ways to engineer them for drug delivery, the investigators report.
“These nanostructured vaults offer a human-friendly nanocontainer, like a molecular-level C-5A transport jet, with a cargo hold large enough to encompass a whole ribosome with its hundreds of proteins and nucleic acids or enough drugs to control a cell,” points out David Eisenberg, Ph.D., of the departments of biological chemistry at UCLA’s Geffen School of Medicine and the California NanoSystems Institute.
Using X-ray diffraction and computer modeling, the team developed a draft atomic model for the major vault protein, which forms the shell-like enclosure of the vault. “Our draft model is essentially an atomic-level vault with a completely unique structure, like a barrel with staves,” explains Leonard H. Rome, Ph.D., who is affiliated with the same institutes as Dr. Eisenberg. “It is unlike any other large structure found in nature.
“The outside of the vault structure is like an eggshell,” Dr. Rome adds, “a continuous protective barrier with no gaps.” The shell is made up of 96 identical protein chains, each made 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.
The research was also conducted by scientists at the Howard Hughes Medical Institute. The study appears in the November 27 edition of PLoS Biology.