Disulfide-Mediated β-Strand Dimers: Hyperstable β-Sheets Lacking Tertiary Interactions and Turns
Brandon L Kier1, Jordan M Anderson1, Niels H Andersen1
1Chemistry Department, University of Washington, Seattle, Washington 98195, United States.
Journal of the American Chemical Society
|April 4, 2015
Summary
Disulfide bonds can nucleate antiparallel beta-sheet structure in peptides. This new method, using strand-central cystines, offers a superior way to design stable beta-sheets without traditional turns.
Area of Science:
- Protein and Peptide Design
- Biophysical Chemistry
- Structural Biology
Background:
- Disulfide bonds are crucial for protein structure and folding.
- Their use in peptide design has mainly involved reinforcing existing structures or creating knots.
- Disulfide bonds at non-H-bonding positions have been used in beta-hairpins for positive controls.
Purpose of the Study:
- To introduce a new class of designed beta-sheet peptide dimers.
- To investigate the role of strand-central disulfides as nucleators of beta-sheet formation.
- To establish design principles for disulfide-tethered 'turnless' beta-sheets.
Main Methods:
- Design and synthesis of short peptides incorporating central disulfide bonds.
- Characterization of beta-sheet structure nucleation and stabilization.
- Comparative analysis of disulfide bonds versus traditional turns in promoting beta-sheet formation.
Main Results:
- A single disulfide bond near the peptide chain's center can nucleate antiparallel beta-sheet structure.
- Addition of beta-capping units and cross-strand interactions leads to hyperstable sheets.
- Strand-central cystines are more effective at nucleating beta-sheet formation than designed reversing turns.
Conclusions:
- Disulfide bonds can serve as effective nucleators for beta-sheet structure.
- This strategy enables the design of stable, 'turnless' beta-sheets.
- Provides a framework and design rules for future applications of disulfide-mediated beta-sheet formation.
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