Pauling first described the α-helix nearly 50 years ago, yet new features of its structure continue to be discovered, using peptide model systems, site-directed mutagenesis, advances in theory, the expansion of the Protein Data Bank and new experimental techniques. Helical peptides in solution form a vast number of structures, including fully helical, fully coiled and partly helical. To interpret peptide results quantitatively it is essential to use a helix/coil model that includes the stabilities of all these conformations. Our models now include terms for helix interiors, capping, side-chain interactions, N-termini and 310-helices. The first three amino acids in a helix (N1, N2 and N3) and the preceding N-cap are unique, as their amide NH groups do not participate in backbone hydrogen bonding. We surveyed their structures in proteins and measured their amino acid preferences. The results are predominantly rationalized by hydrogen bonding to the free NH groups. Stabilizing side-chain-side-chain energies, including hydrophobic interactions, hydrogen bonding and polar/non-polar interactions, were measured accurately in helical peptides. Helices in proteins show a preference for having approximately an integral number of turns so that their N- and C-caps lie on the same side. There are also strong periodic trends in the likelihood of terminating a helix with a Schellman or αL C-cap motif. The kinetics of α-helix folding have been studied with stopped-flow deep ultraviolet circular dichroism using synchrotron radiation as the light source; this gives a far superior signal-to-noise ratio than a conventional instrument. We find that poly(Glu), poly(Lys) and alanine-based peptides fold in milliseconds, with longer peptides showing a transient overshoot in helix content.
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August 2001
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Conference Article|
August 01 2001
Structure, stability and folding of the α-helix
Andrew J. Doig;
Andrew J. Doig
1
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
1To whom correspondence should be addressed.
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Charles D. Andrew;
Charles D. Andrew
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
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Duncan A. E. Cochran;
Duncan A. E. Cochran
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
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Eleri Hughes;
Eleri Hughes
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
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Simon Penel;
Simon Penel
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
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Jia Ke Sun;
Jia Ke Sun
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
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Benjamin J. Stapley;
Benjamin J. Stapley
*Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester M60 1QD, U.K.
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David T. Clarke;
David T. Clarke
†Daresbury Laboratory, Daresbury, Warrington, Cheshire WA4 4AD, U.K.
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Gareth R. Jones
Gareth R. Jones
†Daresbury Laboratory, Daresbury, Warrington, Cheshire WA4 4AD, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2001 The Biochemical Society
2001
Biochem Soc Symp (2001) 68: 95–110.
Citation
Alan Berry, Sheena E. Radford, Andrew J. Doig, Charles D. Andrew, Duncan A. E. Cochran, Eleri Hughes, Simon Penel, Jia Ke Sun, Benjamin J. Stapley, David T. Clarke, Gareth R. Jones; Structure, stability and folding of the α-helix. Biochem Soc Symp 1 August 2001; 68 95–110. doi: https://doi.org/10.1042/bss0680095
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