Dissecting the energetics of protein α-helix C-cap termination through chemical protein synthesis

Duhee Bang, Alexey V. Gribenko, Valentina Tereshko, Anthony A. Kossiakoff, Stephen B. Kent, George I. Makhatadze

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The α-helix is a fundamental protein structural motif and is frequently terminated by a glycine residue. Explanations for the predominance of glycine at the C-cap terminal portions of α-helices have invoked uniquely favorable energetics of this residue in a left-handed conformation or enhanced solvation of the peptide backbone because of the absence of a side chain. Attempts to quantify the contributions of these two effects have been made previously, but the issue remains unresolved. Here we have used chemical protein synthesis to dissect the energetic basis of α-helix termination by comparing a series of ubiquitin variants containing an L-amino acid or the corresponding D-amino acid at the C-cap Gly35 position. D-Amino acids can adopt a left-handed conformation without energetic penalty, so the contributions of conformational strain and backbone solvation can thus be separated. Analysis of the thermodynamic data revealed that the preference for glycine at the C′ position of a helix is predominantly a conformational effect.

Original languageEnglish
Pages (from-to)139-143
Number of pages5
JournalNature Chemical Biology
Issue number3
Publication statusPublished - 2006 Mar


All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Bang, D., Gribenko, A. V., Tereshko, V., Kossiakoff, A. A., Kent, S. B., & Makhatadze, G. I. (2006). Dissecting the energetics of protein α-helix C-cap termination through chemical protein synthesis. Nature Chemical Biology, 2(3), 139-143. https://doi.org/10.1038/nchembio766