The promiscuity of beta-strand pairing allows for rational design of beta-sheet face inversion

J Am Chem Soc. 2008 Nov 5;130(44):14370-1. doi: 10.1021/ja805011h. Epub 2008 Oct 9.

Abstract

Recent studies suggest the dominant role of main-chain H-bond formation in specifying beta-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing beta-sheet-based nanomaterials. Here we show rational design of beta-sheet face inversions by incremental deletions of beta-strands from the single-layer beta-sheet of Borrelia outer surface protein A. We show that a beta-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a beta-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success of the design and supported the importance of main-chain H-bonds in determining beta-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on beta-rich peptide self-assemblies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Bacterial / chemistry*
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacteriophage T4 / enzymology
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Muramidase / chemistry*
  • Peptide Fragments / chemistry
  • Protein Structure, Secondary*

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Peptide Fragments
  • OspB protein, Borrelia burgdorferi
  • Muramidase