The simplest dynamic model for an unfolded protein is a statistical coil that continually undergoes substantial conformational fluctuations. A growing number of studies indicate that the unfolded protein is not a simple random coil but rather forms transient structures. We have directly measured the rate of conformational fluctuations of unfolded intestinal fatty acid binding protein (131aa, 15kDa) by using fluorescence self-quenching in combination with fluorescence correlation spectroscopy. The conformational fluctuations in this state have an apparent relaxation time,τR, of 1.6 μsec in 3 M guanidine-HCl at pH 7 and 20°C. The value of τR increases with increasing solution viscosity, suggesting a diffusive process. In the molten globule state at pH 2, τR is 2.5 μsec, increasing further with the formation of salt-induced secondary structure. These measurements, which should be widely applicable to other systems, can provide important information about the still incompletely understood conformational properties of unfolded proteins and the mechanism of protein folding.

Original languageEnglish
Pages (from-to)2385-2389
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 15 2005


  • Dynamics
  • Fatty acid binding protein
  • Molten globule
  • Relaxation times


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