Rat (Rattus norvegicus)
Vaults are the largest cytoplasmic ribonucleoprotein particles found in numerous eukaryotic species. They were first observed in 1986 as contaminants in preparations of clathrin-coated vesicles from rat liver. Rat liver vault comprises three kind of proteins: the major vault protein (MVP), the vault poly (ADP-ribose) polymerase (VPARP), and the telomerase-associated protein 1 (TEP1) and a small untranslated RNA consisting of 141 bases (vRNA). The mass of rat liver vault is about 10 MDa, and the particle shell measures about 700 angstrom in length and about 400 angstrom in maximum diameter. Most vault particles are present in the cytoplasm, but a few of them (about 5% of the total vault fraction) localize to the nucleus. Several studies suggested that vaults might play an important role in the multidrug resistance (MDR) of cancer cells. Human vRNAs have the ability to bind mitoxantrone, a chemotherapeutic compound, and they may play an important role in the export of toxic compounds (Gopinath et al., Nucleic Acids Res., 33, 4874-4881 (2005)). The recent study showed that vaults may be involved in innate immunity (M. P. Kowalski et al., Science 317, 130-132 (2007)). However, heir cellular function remains unclear.
The x-ray structure of rat liver vault at 3.5 angstrom resolution was shown in Figure 1 (Left) (H. Tanaka et al., Scinece 323, 384-388 (2009)).
X-ray structure reveals that vault particle has 39-fold dihedral symmetry and shell is made up of 78 identical MVP chains. Each MVP monomer folds into 12 domains: nine structural repeat domains, a shoulder domain, a cap-helix domain, and a cap-ring domain (Figure1 (Right)).
Side-by-side hydrophobic interactions of the cap-helix domain play a key role for self-assembly of the vault. The shoulder domain is structurally similar to the core domain of stomatin from Pyrococcus horikoshii (PDBjMine:3bk6), which is involved in lipid raft association. This result supports the report proposing that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, Whole vault structure will be breakthrough in the elucidation of its function.
Protein Data Bank (PDB)
author: Hideaki Tanaka