They are very, VERY large (for intracellular particles, that is), there are hundreds of them most animal’s cells, and we don’t know what they are doing. Meet the vaults.

Vaults are mysterious large ribonucleoprotein (protein and RNA) structures in the cell. Although three times larger than ribosomes, and present in many copies in the cell, they were only discovered in the 1980s. Since their discovery some 25 years ago their cellular function, or functions, are still unclear.

In sea urchins, they have been shown to migrate to the nucleus. Because they are hollow and may fit well in the nuclear pore, some think they may be involved in nuclear transport. They have also been suspected to be associated with Multi Drug Resistance. MDR is an important phenomenon that has to do with sensitivity of tumor cells to cancer drugs. Tumors exhibiting MDR are less responsive to chemotherapy: they break down or remove cytostatic drugs. Vaults have been suspected of being such “drug shuttles” as they seem to be overexpressed in certain cancer cell types or when exposed to cytostatic drugs: drugs that are used to stop cells from dividing, common in cancer chemotherapy. Nevertheless, knockout mice studies have shown that mice where the gene from MVP is knocked are not extra sensitive to cytostatic drugs. However recently it was shown that vault particles may have a role in a related  cellular pathway,  programmed cell death, which may explain why they proliferate in cancer cell line, but do not affect sensitivity to cytostatic drugs that do not induce programmed cell death.

Why “vaults”?  Because when viewed through a longitudinal slice, they resemble a cathedral’s vaulted ceiling (See B, below).

Vault, Cryo-EM

Vault, Cryo-EM micrograph at 33A resolution. From Stewart et al. BMC Developmental Biology 2005 5:3 doi:10.1186/1471-213X-5-3. Clicking on link will take you to the original image in the article. Reproduced under the Creative Commons Attribution License

I am writing about vaults today because a group in Osaka, Japan has recently solved the structure of the vault in 3.5A resolution using X-ray crystallography. This still does not tell us what vault riboproteins do, but it may bring us closer now that we have a solution in atomic resolution. Also we get some really cool images and movies. The full PDB files can be downloaded form their site.  The main “construction unit” of the vault is the Major Vault Protein (MVP). The vault particle is composed from 78 MVPs  laid together as shown in the movie from the same site:

Here is a picture that shows a half vault, each of the 78 MVP chains colored differently, in spectral colors. One is drawn in white, for emphasis; looks a bit like like a Rasta wool cap, really.


Click for full size image. I colored one chain specifically in white, to show how it slants around the vault structure. Drawn using PyMOL

Last pic is of a single MVP chain, colored by secondary structures.

A single MVP.

A single MVP, notice how the repetitive stand (yellow) and loop (green) domains twist in relation to each other. Click for larger picture. Drawn using PyMOL.

So what are we left with? Literally, a big mystery. Very large cellular particles, almost everywhere; they do something, but after 25 years of knowing about them, we’re not sure exactly what. The Rome lab at UCLA has a very informative site about vaults. Happy vaulting.

H. Tanaka, K. Kato, E. Yamashita, T. Sumizawa, Y. Zhou, M. Yao, K. Iwasaki, M. Yoshimura, T. Tsukihara (2009). The Structure of Rat Liver Vault at 3.5 Angstrom Resolution Science, 323 (5912), 384-388 DOI: 10.1126/science.1164975

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One Response to “Vaults”

  1. […] Byte Size Biology covers this paper in an interesting and highly visual post. […]