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Science 13 December 2002:
Vol. 298. no. 5601, pp. 2191 - 2195
DOI: 10.1126/science.1077809
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Reports

Experimental Identification of Downhill Protein Folding

Maria M. Garcia-Mira,12* Mourad Sadqi,1 Niels Fischer,1 Jose M. Sanchez-Ruiz,2 Victor Muñoz1dagger

Theory predicts the existence of barrierless protein folding. Without barriers, folding should be noncooperative and the degree of native structure should be coupled to overall protein stability. We investigated the thermal unfolding of the peripheral subunit binding domain from Escherichia coli's 2-oxoglutarate dehydrogenase multienzyme complex (termed BBL) with a combination of spectroscopic techniques and calorimetry. Each technique probed a different feature of protein structure. BBL has a defined three-dimensional structure at low temperatures. However, each technique showed a distinct unfolding transition. Global analysis with a statistical mechanical model identified BBL as a downhill-folding protein. Because of BBL's biological function, we propose that downhill folders may be molecular rheostats, in which effects could be modulated by altering the distribution of an ensemble of structures.

1 Department of Chemistry and Biochemistry and Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA.
2 Departamento de Química-Física, Facultad de Ciencias, Universidad de Granada, Granada 18071, Spain.
*   Present address: Biochemisches Laboratorium, Universität Bayreuth, D-95412 Bayreuth, Germany.

dagger    To whom correspondence should be addressed. E-mail: vm48{at}umail.umd.edu

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