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Comment
. 2018 Sep 21;293(38):14951-14952.
doi: 10.1074/jbc.H118.005031.

Mallostery: Filling a niche between quality and metabolic control

Ngee Kiat Chua  1 , Andrew J Brown  2
Affiliations
Comment

Mallostery: Filling a niche between quality and metabolic control

Ngee Kiat Chua et al. J Biol Chem. .

Erratum in

Abstract

To be, or not to be … What determines the destruction of a protein in response to metabolic cues? In the current issue of JBC, Wangeline and Hampton shed new light on this existential question by studying the classic case of HMGCR (Hmg2 in yeast), the rate-limiting step in sterol synthesis, and find a metabolic cue that causes "allosteric misfolding" and subsequent destruction of the protein, a concept they name mallostery.

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Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article.

Figures

Figure 1.
Figure 1.
Proposed model of GGPP-mediated degradation of Hmg2 through “allosteric misfolding” or “mallostery.” The model revolves around the idea that local misfolding induced by the potent isoprenoid GGPP sends out a distress signal so that Hmg2 can be degraded. Hmg2 exists as a multimer, which can exist in two different conformations, either the stable native state or the malformed state. Binding of GGPP induces structural changes in Hmg2, which exposes new sites (in green) that increase susceptibility to added proteases. The changes would then lead to degradation by the protein quality control. The chemically similar analog GGSPP can oppose the action of GGPP.
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Comment on

References

    1. Wangeline M. A., Vashistha N., and Hampton R. Y. (2017) Proteostatic tactics in the strategy of sterol regulation. Annu. Rev. Cell Dev. Biol. 33, 467–489 10.1146/annurev-cellbio-111315-125036 - DOI - PMC - PubMed
    1. Johnson B. M., and DeBose-Boyd R. A. (2018) Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase. Semin. Cell Dev. Biol. 81, 121–128 10.1016/j.semcdb.2017.10.019 - DOI - PMC - PubMed
    1. Faust J. R., Luskey K. L., Chin D. J., Goldstein J. L., and Brown M. S. (1982) Regulation of synthesis and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by low density lipoprotein and 25-hydroxycholesterol in UT-1 cells. Proc. Natl. Acad. Sci. U.S.A. 79, 5205–5209 10.1073/pnas.79.17.5205 - DOI - PMC - PubMed
    1. Roitelman J., and Simoni R. D. (1992) Distinct sterol and nonsterol signals for the regulated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase. J. Biol. Chem. 267, 25264–25273 - PubMed
    1. Hampton R. Y., and Rine J. (1994) Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J. Cell Biol. 125, 299–312 10.1083/jcb.125.2.299 - DOI - PMC - PubMed

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