The major vault protein is related to the toxic anion resistance protein (TelA) family.
Vaults are barrel-shaped ribonucleoprotein particles that are abundant in certain tumors and multidrug resistant cancer cells. Prokaryotic relatives of the major vault protein, MVP, have not been identified. We used sequence analysis and molecular modeling to show that MVP and the toxic anion resistance protein, TelA of Rhodobacter sphaeroides strain 2.4.1, share a novel fold that consists of a three-stranded antiparallel beta-sheet. Because of this strong structural correspondence, we examined whether mammalian cell vaults respond to tellurite treatment. In the presence of the oxyanion tellurite, large vault aggregates, or vaultosomes, appear at the cell periphery in 15 min or less. Vaultosome formation is temperature-dependent, reversible, and occurs in normal human umbilical vein endothelial cells as well as transformed HeLa cervical cancer cells. Vaultosome formation is not restricted to tellurite and occurs in the presence of other toxic oxyanions (selenate, selinite, arsenate, arsenite, vanadate). In addition, vaultosomes form independently from other stress-induced ribonucleoprotein complexes, stress granules and aggresomes. Vaultosome formation is therefore a unique cellular response to an environmental toxin.
Suprenant
Kathy A
KA
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. ksupre@ku.edu
Bloom
Nathan
N
Fang
Jianwen
J
Lushington
Gerald
G
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001704:Biopolymers; D002461:Cell Line, Transformed; D022083:Cytoplasmic Structures / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011387:Prokaryotic Cells / Q000737:chemistry; D020836:Protein Structure, Quaternary / Q000187:drug effects; D012242:Rhodobacter sphaeroides / Q000737:chemistry* / Q000187:drug effects; D012261:Ribonucleoproteins / Q000378:metabolism; D013691:Tellurium / Q000494:pharmacology; D020394:Vault Ribonucleoprotein Particles / Q000737:chemistry* / Q000378:metabolism; D000099187:Major Vault Protein
D001426:Bacterial Proteins; D001704:Biopolymers; D011065:Poly(ADP-ribose) Polymerases; D012261:Ribonucleoproteins; D013691:Tellurium; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C449359:vault poly(ADP-ribose) polymerase; C026660:tellurous acid