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The denatured state (the other half of the folding equation) and its role in protein stability
Author(s) -
Shortle David
Publication year - 1996
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.10.1.8566543
Subject(s) - protein folding , folding (dsp implementation) , protein stability , chemistry , native state , protein structure , mutant , stability (learning theory) , state (computer science) , biophysics , crystallography , biochemistry , biology , computer science , algorithm , machine learning , electrical engineering , gene , engineering
Experimental studies of the physical interactions that stabilize protein structure are complicated by the fact that proteins do not unfold to a simple reference state. When their folded structure breaks down, protein chains do not become random coils. Instead, they enter a poorly understood ensemble of partially folded states known collectively as the denatured state. Although it has long been held that agents that promote protein unfolding act specifically oh the denatured state, the idea that mutations can exert their destabilizing (or in some cases, stabilizing) effects directly on this state is not widely accepted. A large body of thermodynamic data on mutant proteins plus a limited amount of structural information describing mutational effects on denatured states indicate that 1) the denatured state plays a central role in all aspects of protein stability, including mutant effects, and 2) a quantitative understanding of how amino acid sequence encodes protein structure will probably depend on a more complete picture of this complex, difficult‐to‐study state.—Shortle, D. The denatured state (the other half of the folding equation) and its role in protein stability. FASEB J. 10, 27‐34 (1996)