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Cofactor effects on the protein folding reaction: Acceleration of α‐lactalbumin refolding by metal ions
Author(s) -
Bushmaritalia A.,
Blanchet Clément E.,
Vernier Grégory,
Forge Vincent
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.051904206
Subject(s) - molten globule , protein folding , lactalbumin , chemistry , cofactor , native state , metal ions in aqueous solution , folding (dsp implementation) , crystallography , folding funnel , affinities , metal , phi value analysis , stereochemistry , biochemistry , downhill folding , organic chemistry , enzyme , electrical engineering , engineering
About 30% of proteins require cofactors for their proper folding. The effects of cofactors on the folding reaction have been investigated with α‐lactalbumin as a model protein and metal ions as cofactors. Metal ions accelerate the refolding of α‐lactalbumin by lessening the energy barrier between the molten globule state and the transition state, mainly by decreasing the difference of entropy between the two states. These effects are linked to metal ion binding to the protein in the native state. Hence, relationships between the metal affinities for the intermediate states and those for the native state are observed. Some residual specificity for the calcium ion is still observed in the molten globule state, this specificity getting closer in the transition state to that of the native state. The comparison between kinetic and steady‐state data in association with the Φ value method indicates the binding of the metal ions on the unfolded state of α‐lactalbumin. Altogether, these results provide insight into cofactor effects on protein folding. They also suggest new possibilities to investigate the presence of residual native structures in the unfolded state of protein and the effects of such structures on the protein folding reaction and on protein stability.