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The role of hydrophobic interactions in initiation and propagation of protein folding

Academic Article
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Overview

authors

  • Dyson, Jane
  • Wright, Peter
  • Scheraga, Harold

publication date

  • August 2006

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Globular proteins fold by minimizing the nonpolar surface that is exposed to water, while simultaneously providing hydrogen-bonding interactions for buried backbone groups, usually in the form of secondary structures such as alpha-helices, beta-sheets, and tight turns. A primary thermodynamic driving force for the formation of globular structure is thus the sequestration of nonpolar groups, but the correlation between the parts of proteins that are observed to fold first (termed folding initiation sites) and the "hydrophobicity" (as customarily defined) of the amino acids in these regions has been quite weak. It has previously been noted that many amino acid side chains contain considerable nonpolar sections, even if they also contain polar or charged groups. For example, a lysine side chain contains four methylenes, which may undergo hydrophobic interactions if the charged epsilon-NH(3)(+) group is salt-bridged or hydrogen-bonded. Folding initiation sites might therefore contain not only accepted "hydrophobic" amino acids, but also larger charged side chains. Recent experiments on the folding of mutant apomyoglobins provides corroboration for models based on the hypothesis that folding initiation sites arise from hydrophobic interactions. A near-perfect correlation was observed between the areas of the molecule that are present in the burst-phase kinetic intermediate and both the free energy of formation of hydrophobic initiation sites and the parameter "average area buried upon folding," which pinpoints large side chains, even those containing charged or polar portions. These results provide a putative mechanism for the control of protein-folding initiation and growth by polar/nonpolar sequence propensity alone.

subject areas

  • Animals
  • Hydrophobic and Hydrophilic Interactions
  • Models, Biological
  • Myoglobin
  • Protein Folding
  • Ribonuclease, Pancreatic
  • Sperm Whale
  • Thermodynamics
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Research

keywords

  • folding pathways
  • myoglobin
  • ribonuclease
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Identity

PubMed Central ID

  • PMC1559752

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0605504103

PubMed ID

  • 16916929
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Additional Document Info

start page

  • 13057

end page

  • 13061

volume

  • 103

issue

  • 35

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