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Folding of insulin-like growth factor I is thermodynamically controlled by insulin-like growth factor binding protein.
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- Hober, Sophia (author)
- KTH,Biokemi och biokemisk teknologi
- Hansson, A (author)
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- Uhlén, Mathias (author)
- KTH,Biokemi och biokemisk teknologi
- show more...
- Nilsson, B (author)
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- (creator_code:org_t)
- 2002-05-01
- 1994
- English.
- In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 33:22
- Journal article (peer-reviewed)
Abstract
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- Insulin-like growth factor I (IGF-I) is thermodynamically unable to quantitatively form its native disulfides under reversible redox conditions in vitro [Hober et al. (1992) Biochemistry 31, 1749-1756]. These results prompted the question of how IGF-I may overcome this energetic problem in its folding in vivo. Here, we report that an IGF-I precursor, IGF-I-Ea, shows disulfide-exchange folding properties similar to those of mature IGF-I and, thus, is concluded not to overcome the identified folding problem of mature IGF-I. However, correct disulfide bonds are formed very efficiently when insulin-like growth factor binding protein 1 is added in equimolar amounts to IGF-I to the refolding mixture. On the basis of these results, we propose that one important function of at least one of the six homologous insulin-like growth factor binding proteins is to assist in the formation and maintenance of the native disulfides of IGF-I. To our knowledge, this is the first example where the folding of a mammalian protein or peptide in circulation has been demonstrated to be thermodynamically controlled by its binding protein. Speculatively, this could provide a mechanism to regulate the half-life of IGF-I in vivo by altering the interaction with insulin-like growth factor binding proteins.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology (hsv//eng)
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- Uhlén, Mathias
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- Biochemistry
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- Royal Institute of Technology
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