skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Aromatic Cross-Strand Ladders Control the Structure and Stability of [beta]-Rich Peptide Self-Assembly Mimics

Abstract

Though {beta}-rich self-assemblies comprise a major structural class of polypeptides, a detailed understanding of the determinants of their structure and stability is lacking. In particular, the roles of repetitive stretches of side chains running the long axis of these {beta}-sheets, termed 'cross-strand ladders,' remain poorly characterized due to the inherently insoluble and heterogeneous nature of self-assemblies. To overcome these experimental challenges, we have established a complementary experimental system termed 'peptide self-assembly mimics' (PSAMs). The PSAMs capture a defined number of self-assembly-like peptide repeats within a soluble {beta}-rich protein, making structural and energetic studies possible. In this work, we investigated the role of cross-strand ladders containing aromatic residues, which are prominent in self-assembling peptides. A combination of solution data and high-resolution crystal structures revealed that a single cross-strand ladder consisting solely of Tyr significantly stabilized, rigidified, and flattened the PSAM {beta}-sheet. These characteristics would stabilize each {beta}-sheet layer of a self-assembly and direct sheet conformations compatible with lamination. Our results therefore provide a rationale for the abundance of aromatic amino acids in fibril-forming peptides and establish important roles of cross-strand Tyr ladders in the structure and stability of {beta}-rich peptide self-assemblies.

Authors:
; ; ;  [1]
  1. UC
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1007130
Resource Type:
Journal Article
Journal Name:
J. Mol. Biol.
Additional Journal Information:
Journal Volume: 383; Journal Issue: (1) ; 10, 2008; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; ABUNDANCE; AMINO ACIDS; AROMATICS; CHAINS; CRYSTAL STRUCTURE; PEPTIDES; POLYPEPTIDES; RESIDUES; STABILITY

Citation Formats

Biancalana, Matthew, Makabe, Koki, Koide, Akiko, and Koide, Shohei. Aromatic Cross-Strand Ladders Control the Structure and Stability of [beta]-Rich Peptide Self-Assembly Mimics. United States: N. p., 2009. Web. doi:10.1016/j.jmb.2008.08.031.
Biancalana, Matthew, Makabe, Koki, Koide, Akiko, & Koide, Shohei. Aromatic Cross-Strand Ladders Control the Structure and Stability of [beta]-Rich Peptide Self-Assembly Mimics. United States. https://doi.org/10.1016/j.jmb.2008.08.031
Biancalana, Matthew, Makabe, Koki, Koide, Akiko, and Koide, Shohei. 2009. "Aromatic Cross-Strand Ladders Control the Structure and Stability of [beta]-Rich Peptide Self-Assembly Mimics". United States. https://doi.org/10.1016/j.jmb.2008.08.031.
@article{osti_1007130,
title = {Aromatic Cross-Strand Ladders Control the Structure and Stability of [beta]-Rich Peptide Self-Assembly Mimics},
author = {Biancalana, Matthew and Makabe, Koki and Koide, Akiko and Koide, Shohei},
abstractNote = {Though {beta}-rich self-assemblies comprise a major structural class of polypeptides, a detailed understanding of the determinants of their structure and stability is lacking. In particular, the roles of repetitive stretches of side chains running the long axis of these {beta}-sheets, termed 'cross-strand ladders,' remain poorly characterized due to the inherently insoluble and heterogeneous nature of self-assemblies. To overcome these experimental challenges, we have established a complementary experimental system termed 'peptide self-assembly mimics' (PSAMs). The PSAMs capture a defined number of self-assembly-like peptide repeats within a soluble {beta}-rich protein, making structural and energetic studies possible. In this work, we investigated the role of cross-strand ladders containing aromatic residues, which are prominent in self-assembling peptides. A combination of solution data and high-resolution crystal structures revealed that a single cross-strand ladder consisting solely of Tyr significantly stabilized, rigidified, and flattened the PSAM {beta}-sheet. These characteristics would stabilize each {beta}-sheet layer of a self-assembly and direct sheet conformations compatible with lamination. Our results therefore provide a rationale for the abundance of aromatic amino acids in fibril-forming peptides and establish important roles of cross-strand Tyr ladders in the structure and stability of {beta}-rich peptide self-assemblies.},
doi = {10.1016/j.jmb.2008.08.031},
url = {https://www.osti.gov/biblio/1007130}, journal = {J. Mol. Biol.},
issn = {0022-2836},
number = (1) ; 10, 2008,
volume = 383,
place = {United States},
year = {Wed Sep 02 00:00:00 EDT 2009},
month = {Wed Sep 02 00:00:00 EDT 2009}
}