Hydrophobic sequence minimization of the alpha-lactalbumin molten globule.
The molten globule, a widespread protein-folding intermediate, can attain a native-like backbone topology, even in the apparent absence of rigid side-chain packing. Nonetheless, mutagenesis studies suggest that molten globules are stabilized by some degree of side-chain packing among specific hydrophobic residues. Here we investigate the importance of hydrophobic side-chain diversity in determining the overall fold of the alpha-lactalbumin molten globule. We have replaced all of the hydrophobic amino acids in the sequence of the helical domain with a representative amino acid, leucine. Remarkably, the minimized molecule forms a molten globule that retains many structural features characteristic of a native alpha-lactalbumin fold. Thus, nonspecific hydrophobic interactions may be sufficient to determine the global fold of a protein.
Wu
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Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA.
Kim
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D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D017421:Sequence Analysis
D007768:Lactalbumin