TY - JOUR

T1 - Conservation of a helix-stabilizing dipole moment in the PP-fold family of regulatory peptides

AU - Bjørnholm, B

AU - Jørgensen, Flemming Steen

AU - Schwartz, T W

PY - 1993

Y1 - 1993

N2 - Investigation of the charge distribution for all known members of the PP-fold family of peptides reveals a common pattern characterized by a cluster of negative charges in the beta-turn region and a cluster of positive charges in the receptor-binding region of the peptide. Detailed analysis of the electrostatic properties of five representative members of the PP-fold family of peptides (human neuropeptide Y, human peptide YY, human pancreatic polypeptide, avian PP, and lamprey peptide methionine tyrosine) shows that this characteristic charge clustering gives rise to a common dipole moment of 325-450 D directed from the beta-turn region toward the receptor-binding region. This overall dipole moment is antiparallel to the dipole moment of the alpha-helix caused by alignment of the peptide dipoles parallel to the helix. Calculations of the stabilization energy for this antiparallel dipole moment arrangement were performed in two ways: (1) by the use of a Poisson-Boltzmann approach which allows for an estimate of the screening effect, and (2) by the use of a uniform dielectric model (Coulomb's law). It is found that the alpha-helix is stabilized by approximately 5-10 kcal/mol due to electrostatic forces alone when the screening effect is considered. This energy is of the same order of magnitude as the enthalpy change for the unfolding of avian PP (approximately 30 kcal/mol), strongly indicating that the charge-dipole interactions are of significant importance for the stability of the three-dimensional structure of the PP-fold peptides.

AB - Investigation of the charge distribution for all known members of the PP-fold family of peptides reveals a common pattern characterized by a cluster of negative charges in the beta-turn region and a cluster of positive charges in the receptor-binding region of the peptide. Detailed analysis of the electrostatic properties of five representative members of the PP-fold family of peptides (human neuropeptide Y, human peptide YY, human pancreatic polypeptide, avian PP, and lamprey peptide methionine tyrosine) shows that this characteristic charge clustering gives rise to a common dipole moment of 325-450 D directed from the beta-turn region toward the receptor-binding region. This overall dipole moment is antiparallel to the dipole moment of the alpha-helix caused by alignment of the peptide dipoles parallel to the helix. Calculations of the stabilization energy for this antiparallel dipole moment arrangement were performed in two ways: (1) by the use of a Poisson-Boltzmann approach which allows for an estimate of the screening effect, and (2) by the use of a uniform dielectric model (Coulomb's law). It is found that the alpha-helix is stabilized by approximately 5-10 kcal/mol due to electrostatic forces alone when the screening effect is considered. This energy is of the same order of magnitude as the enthalpy change for the unfolding of avian PP (approximately 30 kcal/mol), strongly indicating that the charge-dipole interactions are of significant importance for the stability of the three-dimensional structure of the PP-fold peptides.

KW - Amino Acid Sequence

KW - Animals

KW - Birds

KW - Electrochemistry

KW - Humans

KW - Lampreys

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Neuropeptide Y

KW - Pancreatic Polypeptide

KW - Peptide YY

KW - Peptides

KW - Protein Structure, Secondary

KW - Sequence Homology, Amino Acid

KW - Thermodynamics

U2 - 10.1021/bi00063a005

DO - 10.1021/bi00063a005

M3 - Journal article

C2 - 8457560

VL - 32

SP - 2954

EP - 2959

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 12

ER -