The Folding Pathway of Apomyoglobin

  • Patricia A. Jennings
  • H. Jane Dyson
  • Peter E. Wright
Part of the NATO ASI Series book series (NSSB, volume 325)


The detailed molecular mechanism of protein folding is currently a subject of intense interest. It is generally accepted that folding proceeds via the formation of intermediate species rather than through a random conformational search (1) However, the highly cooperative nature of the folding transition for most small proteins precludes structural characterization of intermediate species under equilibrium conditions. Spectroscopic studies of peptide fragments of proteins at equilibrium have been used to help identify regions of a protein with a high propensity to form structure in solution, and thus possible folding initiation sites (2). Kinetic studies of folding reactions have demonstrated the appearance of transient intermediates, but the lifetimes of these species are usually not compatible with detailed structural studies. Nonetheless, stopped-flow studies have provided valuable insights into the formation of folding intermediates. The development of pulsed amide proton exchange experiments in combination with two-dimensional (2D) NMR methods has facilitated the acquisition of detailed structural information on transiently populated folding intermediates (3–10) and has provided considerable impetus to the elucidation of protein folding pathways and the generalized mechanism of protein folding.


Peptide Fragment Amide Proton Hydrogen Exchange Folding Pathway Conformational Preference 
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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Patricia A. Jennings
    • 1
  • H. Jane Dyson
    • 1
  • Peter E. Wright
    • 1
  1. 1.Department of Molecular BiologyThe Scripps Research InstituteLa JollaUSA

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