The major vault protein is the major polypeptide component of a large cellular ribonuclear protein complex found in the cytoplasm of eukaryotic cells (known as vaults). Several roles for vaults have been proposed. Vault proteins have been associated with development of multi-drug resistance []. They have also being implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses [, ].
Vaults are the largest ribonucleoprotein particles known, having a mass of approximately 13 MDa. They are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction and may also play a role in nucleo-cytoplasmic transport. Vaults are present in most normal tissues, but are more highly expressed in epithelial cells with secretory and excretory functions, as well as in cells chronically exposed to xenobiotics, such as bronchial cells and cells lining the intestine []. Overexpression of these proteins is linked with multidrug-resistance in cancer cells.The mammalian vault structure is highly regular and consists of approximately 96 molecules of the 100kDa major vault protein (MVP), 2 molecules of the 240kDa minor vault protein TEP1, 8 molecules of the 193kDa minor vault protein VPARP and at least 6 copies of a small untranslated RNA of 88-141 bases. The MVP molecules form the core of the complex, which is a barrel-like structure with an invaginated waist and two protruding caps. The complex can unfold into two symmetrical flower-like structures with 8 petals each supposedly consisting of 6 MVP molecules []. The MVP protein is composed of two distinct domains []. The N-terminal domain contains ~8 copies of the vault repeat (or MVP repeat) in tandem. The MVP repeat is composed of ~53 amino acids and forms a structural part of the vault wall. The C-terminal part of MVP may be involved in oligomerization and be located in the vault cap, while the MVP repeats in the N-terminal partcan be packed like staves in a barrel to form the vault wall. The 3D structure of the repeat forms a fold that consists of a three stranded (B) antiparallel β-sheet in a unique topology B2-B1-B3 and two loops. MVP repeats can be interaction-mediating modules, as MVP repeats 3 and 4 bind VPARP, which is one of the other vault proteins.
This superfamily represents a repeated domain found in the amino terminal half of the Major Vault Protein (MVP). Vaults are one of the largest cytoplasmic ribonucleoprotein particles, found in numerous eukaryotic species. The cellular function carried out by these ribonucleoproteins remains unclear, although roles in multidrug resistance and innate immunity have been suggested []. The primary sequence of MVP consists of seven short sequence repeats of ~55 amino acid residues followed by a central region and a coiled-coil protein association domain, which mediates the interactions between MVP molecules [].
The vault complex is the largest ribonucleoprotein particle found in eukaryotes []. Although several functions have been proposed for vaults since their discovery in 1986, including roles in multidrug resistance, cell signaling, and innate immunity, their cellular function remains unclear []. In mammals, vaults contain three proteins: the 100kDa major vault protein (MVP), the 193kDa vault poly(ADP-ribosyl)ating polymerase VPARP and the 240kDa telomerase-associated protein TEP1. Approximately 75% of the vault particle mass is due to MVP []. The MVP monomer folds to form structural repeat domains at the N terminus, a shoulder domain, a cap-helix and cap-ring domains.Thissuperfamily represents the major vault protein repeat domain 2, found at the N terminus.
