Abstract
Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains. Recent evidence suggests α-structure is relatively minor among three major backbone conformations for unfolded proteins. The α-helices are the dominant structures in many proteins. For these proteins, how could the α-structures occur from the least in unfolded to the most in folded states? Populations of the minor α-conformation in model peptides provide vital information. Reliable determination of populations of the α-conformers in these peptides that exist in multiple equilibriums of different conformations remains a challenge. Combined analyses on data from AcGXPNH2 and AcGXGNH2 peptides allow us to derive the populations of PII, β and α in AcGXGNH2. Our results show that on average residue X in AcGXGNH2 adopt PII, β, and α 44.7%, 44.5% and 10.8% of time, respectively. The contents of α-conformations for different amino acids define an α-helix nucleation propensity scale. With derived PII, β and α-contents, we can construct a free energy-conformation diagram on each AcGXGNH2 in aqueous solution for the three major backbone conformations. Our results would have broad implications on early-stage events of protein folding.
Highlights
Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains
polyproline II (PII) to βpopulation ratio for each of AcGXPNH2 can be determined; assuming the ratio for X in AcGXPNH2 and AcGXGNH2 is approximately the same, we can derive the population of α-conformer in AcGXGNH2 peptides through equation (1), see Supplementary Information for derivation of the equation in which xα(GXG) denotes the percentage of α-conformer in AcGXGNH2; 3JαN(GXP) and 3JαN(GXG), measured 3JαN coupling constants of X in AcGXPNH2 and AcGXGNH2; 3JαN(α), standard 3JαN coupling constant of a residue in α-helices
Our previous study on AcGGXGGNH2 peptides showed that these peptides are present predominantly in the extended PII or βstructure, around 10% αor turn structures could be present, but the exact percentage of αor turn conformation could not be determined
Summary
Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains. Intrinsic backbone conformational preferences of 20 amino acids determine the local structure of unfolded protein chains; these intrinsic preferences might guide the folding processes at early stages of protein folding. Reliable derivation of populations of the minor α-conformers in model peptides that exist in multiple equilibriums of different backbone conformations remains a challenge[11,18,19,23,24,25,27]. PII to βpopulation ratio for each of AcGXPNH2 can be determined; assuming the ratio for X in AcGXPNH2 and AcGXGNH2 is approximately the same, we can derive the population of α-conformer in AcGXGNH2 peptides through equation (1), see Supplementary Information for derivation of the equation in which xα(GXG) denotes the percentage of α-conformer in AcGXGNH2; 3JαN(GXP) and 3JαN(GXG), measured 3JαN coupling constants of X in AcGXPNH2 and AcGXGNH2; 3JαN(α), standard 3JαN coupling constant of a residue in α-helices
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