Protection of enzymes by alpha-crystallin acting as a molecular chaperone.
How can enzymes function in the centre of a crowded lens over the many decades of an individual's life when the same proteins are usually turned over in a period of days or h in most other tissues? The discovery that alpha-crystallin could function as a molecular chaperone in-vitro has led to the hypothesis that alpha-crystallin could protect enzyme activities against various stresses. In the laboratory the authors have focused on the effect of alpha-crystallin on the activity of enzymes upon exposure to a chemical or thermal stress. The authors have demonstrated that enzymes are rapidly inactivated by sugars, sugar phosphates, steroids and cyanate. These compounds are elevated in diseases such as diabetes, diarrhoea and renal failure, all of which are risk factors for cataract. alpha-Crystallin has been shown to protect specifically against both chemically- and thermally-induced inactivation. Some enzymes are protected with a stoichiometry of one or two enzyme molecules protected per alpha-crystallin aggregate, consistent with a chaperone-like structure. However with other enzymes a more efficient protection occurs consistent with a micellar structure or binding on the outside of alpha-crystallin molecules. Investigation of complex formation indicates that although stable complex formation between enzymes and alpha-crystallin may be involved in protection of enzymes against thermal inactivation, protection against chemically-induced inactivation may be more dynamic in nature.
Hook
D W
DW
Nuffield Laboratory of Ophthalmology, University of Oxford, UK.
Harding
J J
JJ
D000375:Aging / Q000378:metabolism; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002386:Cataract / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D003459:Crystallins / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D046911:Macromolecular Substances; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D003459:Crystallins; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D002374:Catalase