The vault or vault cytoplasmic ribonucleoprotein is a
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' th ...
whose function is not yet fully understood. Discovered and isolated by
Nancy Kedersha
Nancy Kedersha (born 1951) is an American cell biologist and micrographer. She got her Ph.D. from Rutgers University where she worked in Richard Berg's lab studying the characteristics and assembly of prolyl hydroxylases. Afterwards she joined Le ...
and
Leonard Rome in 1986, vaults are cytoplasmic organelles which, when
negative-stained and viewed under an electron microscope, resemble the arches of a cathedral's vaulted ceiling, with 39-fold (or
D39d)
symmetry
Symmetry (from grc, συμμετρία "agreement in dimensions, due proportion, arrangement") in everyday language refers to a sense of harmonious and beautiful proportion and balance. In mathematics, "symmetry" has a more precise definiti ...
.
They are present in many types of eukaryotic cells, and appear to be highly
conserved among
eukaryotes
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacter ...
.
Morphology
Vaults are large
ribonucleoprotein particles. About 3 times the size of a
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to fo ...
and weighing approximately 13 M
Da, they are found in most eukaryotic
cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
and all higher eukaryotes. They measure 34
nm by 60 nm from a
negative stain, 26 nm by 49 nm from
cryo-electron microscopy
Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample so ...
, and 35 nm by 59 nm from
STEM
Stem or STEM may refer to:
Plant structures
* Plant stem, a plant's aboveground axis, made of vascular tissue, off which leaves and flowers hang
* Stipe (botany), a stalk to support some other structure
* Stipe (mycology), the stem of a mushro ...
. The vaults consist primarily of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, making it difficult to stain with conventional techniques.
Structure
The protein structure consists of an outer shell composed of 78 copies of the ~100 kDa
major vault protein
Major vault protein is a protein that in humans is encoded by the ''MVP'' gene. 78 copies of the protein assemble into the large compartments called vaults.
Function
This gene encodes the major vault protein which is a lung infection resista ...
(MVP). Inside are two associated vault proteins,
TEP1 and
VPARP. TEP1, also known as the telomerase-associated protein 1, is 290 kDa and VPARP (also known as PARP4) is related to
poly (ADP-ribose) polymerase (PARP) and is 193 kDa. Vaults from higher eukaryotes also contain one or several small
vault RNAs (vRNAs, also known as vtRNAs) of 86–141 bases within.
The MVP subunits are composed head-to-head, with the N-termini of each half-vault facing each other. From the N-terminal to the C-terminal, a MVP subunit folds into 9 repeat domains, 1 band7-like shoulder domain, 1 cap-helix domain, and 1 cap-ring domain, corresponding to the shape of the vault shell. VPARP is located at repeat domain #4. TEP1, itself a ring due to the
WD40 repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold togeth ...
, binds to the cap domain, with one particular type of vRNA plugging the cap.
Function
Despite not being fully elucidated, vaults have been associated with the
nuclear pore complex
A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complex ...
es and their octagonal shape appears to support this. Vaults have been implicated in a broad range of cellular functions including nuclear-cytoplasmic transport, mRNA localization, drug resistance, cell signaling, nuclear pore assembly, and innate immunity. The three vault proteins (MVP, VPARP, and TEP1) have each been knocked out individually and in combination (VPARP and TEP1) in mice. All of the knockout mice are viable and no major phenotypic alterations have been observed. ''
Dictyostelium
''Dictyostelium'' is a genus of single- and multi-celled eukaryotic, phagotrophic bacterivores. Though they are Protista and in no way fungal, they traditionally are known as "slime molds". They are present in most terrestrial ecosystems ...
'' encode three different MVPs, two of which have been knocked out singly and in combination.
The only phenotype seen in the ''Dictyostelium'' double knockout was growth retardation under nutritional stress.
If vaults are involved in essential cellular functions, it seems likely that redundant systems exist that can ameliorate their loss.
Association with cancer
In the late 1990s, researchers found that vaults (especially the MVP) were over-expressed in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
patients who were diagnosed with
multidrug resistance, that is the resistance against many
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
treatments. Although this does not prove that increased number of vaults led to drug resistance, it does hint at some sort of involvement. This has potential in discovering the mechanisms behind drug-resistance in tumor cells and improving anticancer drugs.
Evolutionary conservation
Vaults have been identified in
mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
,
amphibian
Amphibians are four-limbed and ectothermic vertebrates of the class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terrestrial, fossorial, arbo ...
s,
avians
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...
and ''
Dictyostelium discoideum
''Dictyostelium discoideum'' is a species of soil-dwelling amoeba belonging to the phylum Amoebozoa, infraphylum Mycetozoa. Commonly referred to as slime mold, ''D. discoideum'' is a eukaryote that transitions from a collection of unicellular ...
''.
[ The Vault model used by the ]Pfam
Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 35.0, was released in November 2021 and contains 19,632 families.
Uses ...
database identifies homologues in ''Paramecium tetraurelia
''
''Paramecium'' ( , ; also spelled ''Paramoecium'') is a genus of eukaryotic, unicellular ciliates, commonly studied as a representative of the ciliate group. ''Paramecia'' are widespread in freshwater, brackish, and marine environments and a ...
'', Kinetoplastida, many vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
s, a cnidaria
Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter.
Their distinguishing feature is cnidocytes, specialized cells that ...
n (starlet sea anemone
The starlet sea anemone (''Nematostella vectensis'') is a species of small sea anemone in the family Edwardsiidae native to the east coast of the United States, with introduced populations along the coast of southeast England and the west coast ...
), molluscs, ''Trichoplax adhaerens
''Trichoplax adhaerens'' is one of the three named species in the phylum Placozoa. The others are '' Hoilungia hongkongensis'' and '' Polyplacotoma mediterranea''. The Placozoa is a basal group of multicellular animals (metazoa). ''Trichoplax'' ...
'', flatworm
The flatworms, flat worms, Platyhelminthes, or platyhelminths (from the Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") are a phylum of relatively simple bilaterian, unsegmen ...
s, '' Echinococcus granulosus'' and Choanoflagellate
The choanoflagellates are a group of free-living unicellular and colonial flagellate eukaryotes considered to be the closest living relatives of the animals. Choanoflagellates are collared flagellates, having a funnel shaped collar of interconne ...
.[
http://pfam.xfam.org/family/PF01505 Major Vault Protein repeat Pfam family]
Although vaults have been observed in many eukaryotic species, a few species do not appear to have the ribonucleoprotein. These include:
*''Arabidopsis thaliana
''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land.
A winter ...
''—a small flowering plant related to cabbage and mustard.
*''Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
''—a free-living nematode
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant- parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
that lives in soil.
*''Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
''—a two-winged insect also known as a fruit fly.
*''Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
''—a species of yeast.
These four species are model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
s for plants, nematodes, animal genetics and fungi respectively. Despite these exceptions, the high degree of similarity of vaults in organisms that do have them implies some sort of evolutionary importance.[
Homologs of the major vault protein has been computationally found in bacteria. ]Cyanobacteria
Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, bl ...
l sequences appear most similar. Pfam is also able to identify some such homologs.[
]
Vault engineering
The Rome
, established_title = Founded
, established_date = 753 BC
, founder = King Romulus ( legendary)
, image_map = Map of comune of Rome (metropolitan city of Capital Rome, region Lazio, Italy).svg
, map_caption ...
lab at UCLA has collaborated with a number of groups to use the baculovirus system to produce large quantities of vaults. When the major vault protein
Major vault protein is a protein that in humans is encoded by the ''MVP'' gene. 78 copies of the protein assemble into the large compartments called vaults.
Function
This gene encodes the major vault protein which is a lung infection resista ...
(MVP) is expressed in insect cells, vault particles are assembled on polyribosomes in the cytoplasm. By using molecular genetic techniques to modify the gene encoding the major vault protein, vault particles have been produced with chemically active peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
s attached to their sequence. These modified proteins are incorporated into the inside of the vault particle without altering its basic structure. Proteins and peptides can also be packaged into vaults by attachment of a packaging domain derived from the VPARP protein. A number of modified vault particles have been produced in order to test the concept that vaults can be bio-engineered to allow their use in a wide variety of biological applications including drug delivery, biological sensors, enzyme delivery, controlled release
Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a spe ...
, and environmental remediation
Environmental remediation deals with the removal of pollution or contaminants from environmental media such as soil, groundwater, sediment, or surface water. Remedial action is generally subject to an array of regulatory requirements, and may al ...
.
A vault has been packaged with a chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additi ...
for potential use to activate the immune system to attack lung cancer, and this approach has undergone phase I trials.
See also
* Vault RNA
* Major vault protein
Major vault protein is a protein that in humans is encoded by the ''MVP'' gene. 78 copies of the protein assemble into the large compartments called vaults.
Function
This gene encodes the major vault protein which is a lung infection resista ...
References
External links
Vault website (UCLA)
— Web archive (28 Feb. 2009)
*
*
Major vault protein
on Proteopedia
Proteopedia is a wiki, 3D encyclopedia of proteins and other molecules.
The site contains a page for every entry in the Protein Data Bank (>130,000 pages), as well as pages that are more descriptive of protein structures in general such as acet ...
{{DEFAULTSORT:Vault (Organelle)
Ribonucleoproteins
Organelles