| Hydroimidazolone modification of human alphaA-crystallin: Effect on the chaperone function and protein refolding ability. | |
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MedLine Citation:
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PMID: 20085807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AlphaA-crystallin is a molecular chaperone; it prevents aggregation of denaturing proteins. We have previously demonstrated that upon modification by a metabolic alpha-dicarbonyl compound, methylglyoxal (MGO), alphaA-crystallin becomes a better chaperone. AlphaA-crystallin also assists in refolding of denatured proteins. Here, we have investigated the effect of mild modification of alphaA-crystallin by MGO (with 20-500 microM) on the chaperone function and its ability to refold denatured proteins. Under the conditions used, mildly modified protein contained mostly hydroimidazolone modifications. The modified protein exhibited an increase in chaperone function against thermal aggregation of beta(L)- and gamma-crystallins, citrate synthase (CS), malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) and chemical aggregation of insulin. The ability of the protein to assist in refolding of chemically denatured beta(L)- and gamma-crystallins, MDH and LDH, and to prevent thermal inactivation of CS were unchanged after mild modification by MGO. Prior binding of catalytically inactive, thermally denatured MDH or the hydrophobic probe, 2-p-toluidonaphthalene-6-sulfonate (TNS) abolished the ability of alphaA-crystallin to assist in the refolding of denatured MDH. However, MGO modification of chaperone-null TNS-bound alphaA-crystallin resulted in partial regain of the chaperone function. Taken together, these results demonstrate that: 1) hydroimidazolone modifications are sufficient to enhance the chaperone function of alphaA-crystallin but such modifications do not change its ability to assist in refolding of denatured proteins, 2) the sites on the alphaA-crystallin responsible for the chaperone function and refolding are the same in the native alphaA-crystallin and 3) additional hydrophobic sites exposed upon MGO modification, which are responsible for the enhanced chaperone function, do not enhance alphaA-crystallin's ability to refold denatured proteins. |
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Authors:
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Mahesha H Gangadhariah; Benlian Wang; Mikhail Linetsky; Christian Henning; Robert Spanneberg; Marcus A Glomb; Ram H Nagaraj |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-18 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1802 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-02-22 Completed Date: 2010-04-06 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 432-41 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Crystallins
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chemistry*,
metabolism Humans Hydrophobic and Hydrophilic Interactions Imidazoles / chemistry* Molecular Chaperones / chemistry*, metabolism Protein Denaturation Protein Folding* Protein Structure, Tertiary / physiology |
| Grant Support | |
ID/Acronym/Agency:
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P30 EY011373-139001/EY/NEI NIH HHS; P30EY-11373/EY/NEI NIH HHS; R01 EY009912-14/EY/NEI NIH HHS; R01 EY016219-05/EY/NEI NIH HHS; R01EY-016219/EY/NEI NIH HHS; R01EY-09912/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CRYAA protein, human; 0/Crystallins; 0/Imidazoles; 0/Molecular Chaperones; 0/imidazolone |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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