title: Coassembly of Peptides Derived from β-Sheet Regions of β-Amyloid.
abstract: In this paper, we investigate the coassembly of peptides derived from the central and C-terminal regions of the β-amyloid peptide (Aβ). In the preceding paper, J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b06000 , we established that peptides containing residues 17-23 (LVFFAED) from the central region of Aβ and residues 30-36 (AIIGLMV) from the C-terminal region of Aβ assemble to form homotetramers consisting of two hydrogen-bonded dimers. Here, we mix these tetramer-forming peptides and determine how they coassemble. Incorporation of a single15N isotopic label into each peptide provides a spectroscopic probe with which to elucidate the coassembly of the peptides by1H,15N HSQC. Job's method of continuous variation and nonlinear least-squares fitting reveal that the peptides form a mixture of heterotetramers in 3:1, 2:2, and 1:3 stoichiometries, in addition to the homotetramers. These studies also establish the relative stability of each tetramer and show that the 2:2 heterotetramer predominates.15N-Edited NOESY shows the 2:2 heterotetramer comprises two different homodimers, rather than two heterodimers. The peptides within the heterotetramer segregate in forming the homodimer subunits, but the two homodimers coassemble in forming the heterotetramer. These studies show that the central and C-terminal regions of Aβ can preferentially segregate within β-sheets and that the resulting segregated β-sheets can further coassemble.
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697-2025, United States.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Truex
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697-2025, United States.
authors.forename: James S
authors.initials: JS
authors.lastname: Nowick
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D007536:Isomerism; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D000072757:Protein Conformation, beta-Strand; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments