Native proteins trap high-energy transit conformations
Andrew E. Brereton and P. Andrew Karplus*
- Author Affiliations
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
↵*Corresponding author.
E-mail: karplusp@science.oregonstate.edu
Science Advances 16 Oct 2015: Vol. 1, no. 9, e1501188
Source/Fonte: Science Advances
Abstract
During protein folding and as part of some conformational changes that regulate protein function, the polypeptide chain must traverse high-energy barriers that separate the commonly adopted low-energy conformations. How distortions in peptide geometry allow these barrier-crossing transitions is a fundamental open question. One such important transition involves the movement of a non-glycine residue between the left side of the Ramachandran plot (that is, ϕ < 0°) and the right side (that is, ϕ > 0°). We report that high-energy conformations with ϕ ~ 0°, normally expected to occur only as fleeting transition states, are stably trapped in certain highly resolved native protein structures and that an analysis of these residues provides a detailed, experimentally derived map of the bond angle distortions taking place along the transition path. This unanticipated information lays to rest any uncertainty about whether such transitions are possible and how they occur, and in doing so lays a firm foundation for theoretical studies to better understand the transitions between basins that have been little studied but are integrally involved in protein folding and function. Also, the context of one such residue shows that even a designed highly stable protein can harbor substantial unfavorable interactions.
Keywords ramachandran plot protein folding dipeptide conformation conformational transition peptide geometry strain protein stability transition state disallowed conformation
Copyright © 2015, The Authors
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