Dataset Information

Folding of beta pep-4 beta-sheet sandwich dimers and tetramers is influenced by aliphatic hydrophobic residues at the intersubunit interface.

ABSTRACT: For the designed peptide 33mer, beta pep-4, formation of beta-sheet structure [Ilyina, Roongta and Mayo (1997) Biochemistry 36, 5245--5250] is thermodynamically linked to self-association. Dimers and tetramers are stabilized by interactions between hydrophobic residues lying on the hydrophobic faces of the amphipathic monomer subunits. The present study investigates the effects on folding and self-association of the substitution of two key hydrophobic residues (Ile(20) and Val(22)) at the beta-sheet sandwich interface of beta pep-4. Single-site (I20L, I20V, I20A, V22L, V22I and V22A; where I20L corresponds to the substitution of Ile(20) with leucine etc.) and double-site (I20L/V22L and I20V/V22I) variants have been investigated. Like parent beta pep-4, all variants can form dimers and tetramers. NOESY data indicate that the overall beta-sheet fold and intersubunit beta-strand alignments are the same in all variant tetramers. CD data for all variants indicate mostly beta-sheet character in dimers and random coil character in monomers. Only for the V22I variant is the beta-sheet fold stabilized in the monomer state. Pulse-field gradient NMR-derived diffusion coefficients, measured as a function of peptide concentration, provide a means for deriving the distribution of monomer, dimer and tetramer states and, therefore, equilibrium association constants. Relative thermodynamic stabilities, which vary no more than approx. 0.5 kcal/mol (where 1 kcal identical with 4.184 kJ) from peptide to peptide, are I20V/V22I>I20V>I20L/V22L=beta pep-4 (Delta G(D) of 7.5 kcal/mol)=I20L=I20A>V22I>V22L>V22A for dimer formation and I20V>I20L/V22L>I20L>beta pep-4 (Delta G(T) of 6 kcal/mol)>V22I>I20V/V22I>V22L>I20A>V22A for tetramer formation. For the most part, dimer and/or tetramer stabilities are enhanced by the presence of valine and leucine and are attenuated by the presence of isoleucine and alanine.

SUBMITTER: Cox A

PROVIDER: S-EPMC1222003 | biostudies-other | 2001 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self-assemble into β-sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self-assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac-(XKXE)2 -NH2 peptides (X = hydrophobic residue). A series of Ac-(XKXE)2 -NH2 peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1-naphthylalanine [1-Nal], 2-naphthylalanine [2-Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self-assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac-X1 KFEFKFE-NH2 and Ac-(X1,5 KFE)-NH2 peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy indicated β-sheet formation for all variants. Self-assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self-assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac-(XKXE)2 -NH2 peptides correlates to self-assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self-assembled amphipathic peptides as functional biomaterials.

Dataset Information

Folding of beta pep-4 beta-sheet sandwich dimers and tetramers is influenced by aliphatic hydrophobic residues at the intersubunit interface.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets