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Science 20 July 2001:
Vol. 293. no. 5529, pp. 487 - 489
DOI: 10.1126/science.1060438
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Reports

Persistence of Native-Like Topology in a Denatured Protein in 8 M Urea

David Shortle,* Michael S. Ackerman

Experimental methods have demonstrated that when a protein unfolds, not all of its structure is lost. Here we report measurement of residual dipolar couplings in denatured forms of the small protein staphylococcal nuclease oriented in strained polyacrylamide gels. A highly significant correlation among the dipolar couplings for individual residues suggests that a native-like spatial positioning and orientation of chain segments (topology) persists to concentrations of at least 8 molar urea. These data demonstrate that long-range ordering can occur well before a folding protein attains a compact conformation, a conclusion not anticipated by any of the standard models of protein folding.

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: shortle{at}welchlink.welch.jhu.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)