A model of dynamic side-chain--side-chain interactions in the alpha-lactalbumin molten globule.
Proteins in the molten globule state contain high levels of secondary structure, as well as a rudimentary, nativelike tertiary topology. Thus, the structural similarity between the molten globule and native proteins may have a significant bearing in understanding the protein-folding problem. To explore the nature of side-chain--side-chain interactions in the alpha-lactalbumin (alpha-LA) molten globule, we determined the effective concentration for formation of the 28--111 disulfide bond in 14 double-mutant proteins, each containing two hydrophobic core residues replaced by alanine. We compared our results with those of single-alanine substitutions using the framework of double-mutant cycle analysis and found that, in the majority of cases, the effects of two alanine substitutions are additive. Based on these results, we propose a model of side-chain-side-chain interactions in the alpha-LA molten globule, which takes into consideration the dynamic nature of this partially folded species.
Department of Biochemistry, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
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Bai
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Song
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Luo
Z Y
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Peng
D000409:Alanine; D019943:Amino Acid Substitution; D004926:Escherichia coli; D007768:Lactalbumin / Q000737:chemistry* / Q000235:genetics; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation; D015202:Protein Engineering; D017510:Protein Folding
D007768:Lactalbumin; D000409:Alanine