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Institute for Biological Instrumentation, Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia; Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA
Reprint requests to: Vladimir N. Uversky, Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA; e-mail: uversky{at}hydrogen.ucsc.edu; fax: (831) 459-2935.
Abstract
The experimental material accumulated in the literature on the conformational behavior of intrinsically unstructured (natively unfolded) proteins was analyzed. Results of this analysis showed that these proteins do not possess uniform structural properties, as expected for members of a single thermodynamic entity. Rather, these proteins may be divided into two structurally different groups: intrinsic coils, and premolten globules. Proteins from the first group have hydrodynamic dimensions typical of random coils in poor solvent and do not possess any (or almost any) ordered secondary structure. Proteins from the second group are essentially more compact, exhibiting some amount of residual secondary structure, although they are still less dense than native or molten globule proteins. An important feature of the intrinsically unstructured proteins is that they undergo disorder–order transition during or prior to their biological function. In this respect, the Protein Quartet model, with function arising from four specific conformations (ordered forms, molten globules, premolten globules, and random coils) and transitions between any two of the states, is discussed.
Keywords: Intrinsically unfolded protein; intrinsically disordered protein; unfolded protein; molten globule; premolten globule; partially folded intermediate; random coil; conformational transition
Abbreviations: NMR, nuclear magnetic resonance • CD, circular dichroism • UV, ultraviolet • ORD, optical rotatory dispersion • FTIR, Fourier-transform infrared • SAXS, small-angle X-ray scattering • SANS, small-angle neutron scattering • FRET, fluorescence resonance energy transfer • N, native • MG, molten globule • PMG, premolten globule • U, unfolded • NU, natively unfolded • NUcoil, natively unfolded proteins with coil-like properties • NUPMG, natively unfolded proteins with PMG-like properties
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