Herbert, AP;
Riesen, M;
Bloxam, L;
Kosmidou, E;
Wareing, BM;
Johnson, JR;
Phelan, MM;
... Morgan, A; + view all
(2012)
NMR structure of Hsp12, a protein induced by and required for dietary restriction-induced lifespan extension in yeast.
PLoS One
, 7
(7)
, Article e41975. 10.1371/journal.pone.0041975.
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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 hsp12Δ 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.
| Type: | Article |
|---|---|
| Title: | NMR structure of Hsp12, a protein induced by and required for dietary restriction-induced lifespan extension in yeast. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0041975 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0041975 |
| Language: | English |
| Additional information: | © Herbert et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by a Biotechnology and Biological Sciences Research Council research grant to AM and SRP (Grant Ref ERA16235; funder’s URL http://www.bbsrc.ac.uk/home/home.aspx), a Wellcome Trust project grant to AM and LYL (Grant Ref 090077/Z/09/Z; funder’s URL http://www.wellcome.ac.uk/), and Wellcome Trust Prize Studentships to MR and LB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Gene Expression Regulation, Fungal, Glucose, Heat-Shock Proteins, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Phenotype, Protein Structure, Secondary, Proteomics, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1377995 |
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