Aromatic Cross-Strand Ladders Control the Structure and Stability of [beta]-Rich Peptide Self-Assembly Mimics
- UC
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.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007130
- Journal Information:
- J. Mol. Biol., Journal Name: J. Mol. Biol. Journal Issue: (1) ; 10, 2008 Vol. 383; ISSN JMOBAK; ISSN 0022-2836
- Country of Publication:
- United States
- Language:
- ENGLISH
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