Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress can have profound effects on the cell. The elicitation of the stress response in the cell is often accompanied by the synthesis of high-molecular-mass complexes, sometimes termed heat shock granules (HSGs). The presence of the complexes has been shown to be important for the survival of cells subjected to stress. We purified these complexes from heat-stressed BY-2 tobacco cells. HSG complexes formed in vivo contain predominantly smHSPs, HSP40 and HSP70 and display chaperone-like activity. Tubulins as well as other proteins may be part of the complex or its substrate. The proteins, except smHSPs and to some extent HSP70, were hypersensitive to proteolysis, suggesting that they were partially denatured and not an integral part of the HSG complexes. When citrate synthase was used as the substrate, in vivo generated HSG complexes exhibited strong nucleotide-dependent in vitro chaperone activity. Measurable ATP-mediated hydrolytic activity was detected. Isolated HSG complexes are stable until ATP is added, which leads to rapid dissociation of the complex into subunits. It is proposed that smHSPs form the core of the complex in association with ATP-dependent HSP70 and HSP40 cochaperones. Implications of these findings are discussed.
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PMID:High-molecular-mass complexes formed in vivo contain smHSPs and HSP70 and display chaperone-like activity. 1075 42

alpha-Crystallin, a major lens protein of approximately 800 kDa with subunits of approximately 20 kDa has previously been shown to act as a chaperone protecting other proteins from stress-induced aggregation. Here it is demonstrated that alpha-crystallin can bind to partially denatured enzymes at 42-43 degrees C and prevent their irreversible aggregation, but cannot prevent loss of enzyme activity. However, the alpha-crystallin-bound enzymes regain activity on interaction with other chaperones. The data indicate that the re-activated enzymes are no longer associated with the alpha-crystallin, and ATP is required for re-activation. When inactive luciferase bound to alpha-crystallin was treated with reticulocyte lysate, a rich source of chaperones, up to 60% of the original luciferase activity could be recovered. Somewhat less re-activation was observed when the alpha-crystallin-bound enzyme was treated with heat-shock protein (HSP)70, HSP40, HSP60 and an ATP-generating system. Similar results were also obtained with citrate synthase. The overall results suggest that alpha-crystallin acts to stabilize denaturing proteins so that they can later be re-activated by other chaperones.
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PMID:alpha-crystallin prevents irreversible protein denaturation and acts cooperatively with other heat-shock proteins to renature the stabilized partially denatured protein in an ATP-dependent manner. 1090 3