Structures of single-layer β-sheet proteins evolved from β-hairpin repeats

Protein Sci. 2019 Sep;28(9):1676-1689. doi: 10.1002/pro.3683. Epub 2019 Aug 2.


Free-standing single-layer β-sheets are extremely rare in naturally occurring proteins, even though β-sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single-layer, anti-parallel β-sheet proteins, comprised of three or four twisted β-hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of β-sheets, additional hydrophobic interactions mediated by small clusters of residues adjacent to the turns likely play a significant role in the structural stability and compensate for the lack of a compact hydrophobic core. These structures enabled identification of a family of secreted proteins that are broadly distributed in bacteria from the human gut microbiome and are putatively involved in the metabolism of complex carbohydrates. A conserved surface patch, rich in solvent-exposed tyrosine residues, was identified on the concave surface of the β-sheet. These new modular single-layer β-sheet proteins may serve as a new model system for studying folding and design of β-rich proteins.

Keywords: human gut microbiome; protein folding; secreted proteins; single-layer β-sheet proteins; structural genomics; β-hairpin repeats.

Publication types

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

MeSH terms

  • Bacteria / chemistry
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry*
  • Crystallography, X-Ray
  • Gastrointestinal Microbiome
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Protein Conformation, beta-Strand
  • Protein Folding
  • Tyrosine / chemistry


  • Bacterial Proteins
  • Tyrosine