Vault (organelle)

Source: Wikipedia, the free encyclopedia.
Vault, N-terminal repeat domain
Structure of the Vault complex from rat liver.[1]
Identifiers
SymbolVault
PfamPF01505
InterProIPR002499
PROSITEPDOC51224
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB2ZUO 2ZV4 2ZV5

The vault or vault cytoplasmic ribonucleoprotein is a

eukaryotes.[3]

Morphology

Vaults are large

cryo-electron microscopy, and 35 nm by 59 nm from STEM.[4] The vaults consist primarily of proteins
, 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

VPARP. TEP1, also known as the telomerase-associated protein 1,[5] is 290 kDa and VPARP (also known as PARP4) is related to poly (ADP-ribose) polymerase (PARP) and is 193 kDa.[6] Vaults from higher eukaryotes also contain one or several small vault RNAs (vRNAs, also known as vtRNAs) of 86–141 bases within.[7]

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 binds to repeat domain #4. TEP1, itself a ring due to the WD40 repeat, binds to the cap domain, with one particular type of vRNA plugging the cap.[8]

Function

Despite not being fully elucidated, vaults have been associated with the

nuclear pore complexes and their octagonal shape appears to support this.[9][10] 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.[11] The three vault proteins (MVP, VPARP, and TEP1) have each been knocked out individually and in combination (VPARP and TEP1) in mice.[12][13][14] All of the knockout mice are viable and no major phenotypic alterations have been observed. Dictyostelium encode three different MVPs, two of which have been knocked out singly and in combination.[15] The only phenotype seen in the Dictyostelium double knockout was growth retardation under nutritional stress.[16]
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 patients who were diagnosed with multidrug resistance, that is the resistance against many chemotherapy treatments.[17] 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.[15]

Evolutionary conservation

Vaults have been identified in

mammals, amphibians, avians and Dictyostelium discoideum.[3] The Vault model used by the Pfam database identifies homologues in Paramecium tetraurelia, Kinetoplastida, many vertebrates, a cnidarian (starlet sea anemone), molluscs, Trichoplax adhaerens, flatworms, Echinococcus granulosus and Choanoflagellate.[18]

Although vaults have been observed in many eukaryotic species, a few species do not appear to have the ribonucleoprotein. These include:[19]

These four species are model organisms 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.[3]

Homologs of the major vault protein has been computationally found in bacteria. Cyanobacterial sequences appear most similar.[20][21] Pfam is also able to identify some such homologs.[18]

Vault engineering

The

controlled release, and environmental remediation
.

A vault has been packaged with a chemokine for potential use to activate the immune system to attack lung cancer, and this approach has undergone phase I trials.[23][24]

See also

References

  1. ^
    S2CID 2072790
    .
  2. PMID 2943744
    .
  3. ^
    PMID 1691193
    .
  4. PMID 1988458
    .
  5. PMID 10551828
    .
  6. PMID 10477748
    .
  7. S2CID 21196262
    .
  8. PMID 23060231
    .
  9. PMID 8270627
    .
  10. PMID 7068761
    .
  11. S2CID 6326163
    .
  12. PMID 11149928
    .
  13. PMID 11027287
    .
  14. PMID 12499273
    .
  15. ^
    PMID 15157468
    .
  16. ^
    PMID 23267674
    .
  17. PMID 14576851
    .
  18. ^ a b http://pfam.xfam.org/family/PF01505 Major Vault Protein repeat Pfam family
  19. PMID 14731565
    .
  20. PMID 23887922
    .
  21. bioRxiv 10.1101/872010
    .
  22. PMID 25354757
    .
  23. PMID 25264541
    .
  24. PMID 21559281
    .

External links
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