Kumar, Navinder and Gaur, Deepika and Masison, Daniel C and Sharma, Deepak (2014) The BAG homology domain of Snl1 cures yeast prion [URE3] through regulation of Hsp70 chaperones. G3 (Bethesda, Md.), 4 (3). pp. 461-70. ISSN 2160-1836
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The BAG family of proteins is evolutionarily conserved from yeast to humans and plants. In animals and plants, the BAG family possesses multiple members with overlapping and distinct functions that regulate many cellular processes, such as signaling, protein degradation, and stress response. The only BAG domain protein in Saccharomyces cerevisiae is Snl1, which is anchored to the endoplasmic reticulum through an amino-terminal transmembrane region. Snl1 is the only known membrane-associated nucleotide exchange factor for 70-kilodalton heat shock protein (Hsp70), and thus its role in regulating cytosolic Hsp70 functions is not clear. Here, we examine whether Snl1 regulates Hsp70 activity in the propagation of stable prion-like protein aggregates. We show that unlike other nucleotide exchange factors, Snl1 is not required for propagation of yeast prions [URE3] and [PSI(+)]. Overexpressing Snl1 derivative consisting of only the BAG domain (Snl1-S) cures [URE3]; however, elevated levels of the entire cytosolic domain of Snl1 (Snl1-M), which has nine additional amino-terminal residues, has no effect. Substituting the three lysine residues in this region of Snl1-M with alanine restores ability to cure [URE3]. [PSI(+)] is unaffected by overproduction of either Snl1-S or Snl1-M. The Snl1-S mutant engineered with weaker affinity to Hsp70 does not cure [URE3], indicating that curing of [URE3] by Snl1-S requires Hsp70. Our data suggest that Snl1 anchoring to endoplasmic reticulum or nuclear membrane restricts its ability to modulate cytosolic activities of Hsp70 proteins. Furthermore, the short amino-terminal extension of the BAG domain profoundly affects its function.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Genetics Society of America |
| Uncontrolled Keywords: | Hsp70; nucleotide exchange factor; yeast prion; Snl1; BAG domain |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 20 Jul 2015 03:51 |
| Last Modified: | 20 Jul 2015 03:51 |
| URI: | http://crdd.osdd.net/open/id/eprint/1707 |
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