title: Dissecting the energetics of protein alpha-helix C-cap termination through chemical protein synthesis.
abstract: The alpha-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 alpha-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 alpha-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.
authors.affiliation: Institute for Biophysical Dynamics, Center for Integrative Science, 929 East 57th Street, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Duhee
authors.initials: D
authors.lastname: Bang
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Gribenko
authors.forename: Valentina
authors.initials: V
authors.lastname: Tereshko
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Kossiakoff
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kent
authors.forename: George I
authors.initials: GI
authors.lastname: Makhatadze
mesh_terms: D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D011506:Proteins