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Review
. 2008 Jan 23;27(2):328-35.
doi: 10.1038/sj.emboj.7601970.

Chaperones in control of protein disaggregation

Krzysztof Liberek  1 , Agnieszka Lewandowska, Szymon Zietkiewicz
Affiliations
Review

Chaperones in control of protein disaggregation

Krzysztof Liberek et al. EMBO J. .

Abstract

The chaperone protein network controls both initial protein folding and subsequent maintenance of proteins in the cell. Although the native structure of a protein is principally encoded in its amino-acid sequence, the process of folding in vivo very often requires the assistance of molecular chaperones. Chaperones also play a role in a post-translational quality control system and thus are required to maintain the proper conformation of proteins under changing environmental conditions. Many factors leading to unfolding and misfolding of proteins eventually result in protein aggregation. Stress imposed by high temperature was one of the first aggregation-inducing factors studied and remains one of the main models in this field. With massive protein aggregation occurring in response to heat exposure, the cell needs chaperones to control and counteract the aggregation process. Elimination of aggregates can be achieved by solubilization of aggregates and either refolding of the liberated polypeptides or their proteolysis. Here, we focus on the molecular mechanisms by which heat-shock protein 70 (Hsp70), Hsp100 and small Hsp chaperones liberate and refold polypeptides trapped in protein aggregates.

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Figures

Figure 1
Figure 1
Model for the mechanism of action of Hsp70 and Hsp100 chaperone system in disaggregation of protein aggregates. First, the Hsp70 chaperone system disentangles the polypeptides from aggregates. The polypeptides are then transferred to ClpB/Hsp104 and unfolded by translocation through the central channel, driven by energy from ATP hydrolysis. The unfolded polypeptides are released following translocation and refold either spontaneously or with the assistance of chaperones. The Hsp70 chaperone system and ClpB/Hsp104 cooperate in the disaggregation process in a specific way (marked with the red arrow). The interaction is linked to the propeller-shaped middle domain of ClpB.
Figure 2
Figure 2
The Hsp100, Hsp70 and sHsps chaperones control the fate of aggregation-prone proteins under stress conditions.
See this image and copyright information in PMC

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References

    1. Albanèse V, Yen-Wen Yam A, Baughman J, Parnot C, Frydman J (2006) Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124: 75–88 - PubMed
    1. Allen SP, Polazzi JO, Gierse JK, Easton AM (1992) Two novel heat shock genes encoding proteins produced in response to heterologous protein expression in Escherichia coli. J Bacteriol 174: 6938–6947 - PMC - PubMed
    1. Ammelburg M, Frickey T, Lupas AN (2006) Classification of AAA+ proteins. J Struct Biol 156: 2–11 - PubMed
    1. Barnett ME, Nagy M, Kedzierska S, Zolkiewski M (2005) The amino-terminal domain of ClpB supports binding to strongly aggregated proteins. J Biol Chem 280: 34940–34945 - PubMed
    1. Basha E, Lee GJ, Breci LA, Hausrath AC, Buan NR, Giese KC, Vierling E (2004) The identity of proteins associated with a small heat shock protein during heat stress in vivo indicates that these chaperones protect a wide range of cellular functions. J Biol Chem 279: 7566–7575 - PubMed

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