4AXP: NMR Structure of Hsp12, a Protein Induced by and Required for Dietary Restriction-induced Lifespan Extension in Yeast

Citation:
Abstract
Dietary restriction (DR) extends lifespan in yeast, worms, flies and mammals, suggesting that it may act via conserved processes. However, the downstream mechanisms by which DR increases lifespan remain unclear. We used a gel based proteomic strategy to identify proteins whose expression was induced by DR in yeast and thus may correlate with longevity. One protein up-regulated by DR was Hsp12, a small heat shock protein induced by various manipulations known to retard ageing. Lifespan extension by growth on 0.5% glucose (DR) was abolished in an hsp12Delta strain, indicating that Hsp12 is essential for the longevity effect of DR. In contrast, deletion of HSP12 had no effect on growth under DR conditions or a variety of environmental stresses, indicating that the effect of Hsp12 on lifespan is not due to increased general stress resistance. Unlike other small heat shock proteins, recombinant Hsp12 displayed negligible in vitro molecular chaperone activity, suggesting that its cellular function does not involve preventing protein aggregation. NMR analysis indicated that Hsp12 is monomeric and intrinsically unfolded in solution, but switches to a 4-helical conformation upon binding to membrane-mimetic SDS micelles. The structure of micelle-bound Hsp12 reported here is consistent with its recently proposed function as a membrane-stabilising 'lipid chaperone'. Taken together, our data suggest that DR-induced Hsp12 expression contributes to lifespan extension, possibly via membrane alterations.
PDB ID: 4AXPDownload
MMDB ID: 101829
PDB Deposition Date: 2012/6/13
Updated in MMDB: 2012/08 
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 4AXP: monomeric; determined by software (PQS)
Molecular Components in 4AXP
Label Count Molecule
Protein (1 molecule)
1
12 KDA Heat Shock Protein
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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