Folding of insulin-like growth factor I is thermodynamically controlled by insulin-like growth factor binding protein.

NR 20160331
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.

Hansson, A (författare)
Uhlén, MathiasKTH,Biokemi och biokemisk teknologi(Swepub:kth)u1dulvmw (författare)
Nilsson, B (författare)
KTHBiokemi och biokemisk teknologi (creator_code:org_t)

Av författaren/redakt...: Hober, Sophia; Hansson, A; Uhlén, Mathias; Nilsson, B

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