Abstract
Knowing the partitioning free energy of unfolded polypeptides into membrane interfaces is necessary for understanding membrane protein stability and for designing antimicrobial and other peptides. Experiment-based whole-residue free-energy (hydropathy) scales for amino acids in unfolded peptides, derived from the partitioning of host-guest pentapeptides (Ac-WLXLL) into the interfaces of phosphatidylcholine bilayers and into n-octanol, have been determined by W. C. Wimley, S. H. White, and colleagues [(1996) Nat. Struc. Biol. 3, 842; Wimley, W. C. et al. (1996) Biochemistry 35, 5109]. These scales offer the possibility of computing absolute partitioning free energies of unfolded peptides given only their amino acid sequences. However, the scales are incomplete, because partitioning free energies of N- and C-terminal groups are missing. To complete the scales, we have measured the pH-dependent partitioning of the host-guest pentapeptide variants AcWL-X-LL-NH2 and WL-X-LL-NH2 (X = G or W) into palmitoyloleoylphosphatidylcholine (POPC) bilayer interfaces and n-octanol. These measurements, in combination with the earlier ones, lead to hydrophobicity scale values for protonation, deprotonation, or acetylation of the N terminus and protonation, deprotonation, or amidation of the C terminus. A surprising finding is that a charged N terminus has a much smaller effect on bilayer partitioning than a charged C terminus. We present a simple algorithm for computing the absolute partitioning free energies of unfolded peptides into the phosphatidylcholine bilayer interface.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12614-12619 |
| Number of pages | 6 |
| Journal | Biochemistry® |
| Volume | 44 |
| Issue number | 37 |
| DOIs | |
| State | Published - Sep 20 2005 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
An experiment-based algorithm for predicting the partitioning of unfolded peptides into phosphatidylcholine bilayer interfaces. / Hristova, Kalina A; White, Stephen H.
In: Biochemistry®, Vol. 44, No. 37, 20.09.2005, p. 12614-12619.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An experiment-based algorithm for predicting the partitioning of unfolded peptides into phosphatidylcholine bilayer interfaces
AU - Hristova, Kalina A
AU - White, Stephen H.
PY - 2005/9/20
Y1 - 2005/9/20
N2 - Knowing the partitioning free energy of unfolded polypeptides into membrane interfaces is necessary for understanding membrane protein stability and for designing antimicrobial and other peptides. Experiment-based whole-residue free-energy (hydropathy) scales for amino acids in unfolded peptides, derived from the partitioning of host-guest pentapeptides (Ac-WLXLL) into the interfaces of phosphatidylcholine bilayers and into n-octanol, have been determined by W. C. Wimley, S. H. White, and colleagues [(1996) Nat. Struc. Biol. 3, 842; Wimley, W. C. et al. (1996) Biochemistry 35, 5109]. These scales offer the possibility of computing absolute partitioning free energies of unfolded peptides given only their amino acid sequences. However, the scales are incomplete, because partitioning free energies of N- and C-terminal groups are missing. To complete the scales, we have measured the pH-dependent partitioning of the host-guest pentapeptide variants AcWL-X-LL-NH2 and WL-X-LL-NH2 (X = G or W) into palmitoyloleoylphosphatidylcholine (POPC) bilayer interfaces and n-octanol. These measurements, in combination with the earlier ones, lead to hydrophobicity scale values for protonation, deprotonation, or acetylation of the N terminus and protonation, deprotonation, or amidation of the C terminus. A surprising finding is that a charged N terminus has a much smaller effect on bilayer partitioning than a charged C terminus. We present a simple algorithm for computing the absolute partitioning free energies of unfolded peptides into the phosphatidylcholine bilayer interface.
AB - Knowing the partitioning free energy of unfolded polypeptides into membrane interfaces is necessary for understanding membrane protein stability and for designing antimicrobial and other peptides. Experiment-based whole-residue free-energy (hydropathy) scales for amino acids in unfolded peptides, derived from the partitioning of host-guest pentapeptides (Ac-WLXLL) into the interfaces of phosphatidylcholine bilayers and into n-octanol, have been determined by W. C. Wimley, S. H. White, and colleagues [(1996) Nat. Struc. Biol. 3, 842; Wimley, W. C. et al. (1996) Biochemistry 35, 5109]. These scales offer the possibility of computing absolute partitioning free energies of unfolded peptides given only their amino acid sequences. However, the scales are incomplete, because partitioning free energies of N- and C-terminal groups are missing. To complete the scales, we have measured the pH-dependent partitioning of the host-guest pentapeptide variants AcWL-X-LL-NH2 and WL-X-LL-NH2 (X = G or W) into palmitoyloleoylphosphatidylcholine (POPC) bilayer interfaces and n-octanol. These measurements, in combination with the earlier ones, lead to hydrophobicity scale values for protonation, deprotonation, or acetylation of the N terminus and protonation, deprotonation, or amidation of the C terminus. A surprising finding is that a charged N terminus has a much smaller effect on bilayer partitioning than a charged C terminus. We present a simple algorithm for computing the absolute partitioning free energies of unfolded peptides into the phosphatidylcholine bilayer interface.
UR - http://www.scopus.com/inward/record.url?scp=24944516963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24944516963&partnerID=8YFLogxK
U2 - 10.1021/bi051193b
DO - 10.1021/bi051193b
M3 - Article
C2 - 16156674
AN - SCOPUS:24944516963
VL - 44
SP - 12614
EP - 12619
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 37
ER -