Beta-strand flipping and slipping triggered by turn replacement reveal the opportunistic nature of beta-strand pairing

J Am Chem Soc. 2007 Nov 28;129(47):14661-9. doi: 10.1021/ja074252c. Epub 2007 Nov 7.


We investigated how the register between adjacent beta-strands is specified using a series of mutants of the single-layer beta-sheet (SLB) in Borrelia OspA. The single-layer architecture of this system eliminates structural restraints imposed by a hydrophobic core, enabling us to address this question. A critical turn (turn 9/10) in the SLB was replaced with a segment with an intentional structural mismatch. Its crystal structure revealed a one-residue insertion into the central beta-strand (strand 9) of the SLB. This insertion triggered a surprisingly large-scale structural rearrangement: (i) the central strand (strand 9) was shifted by one residue, causing the strand to flip with respect to the adjacent beta-strands and thus completely disrupting the native side-chain contacts; (ii) the three-residue turn located on the opposite end of the beta-strand (turn 8/9) was pushed into its preceding beta-strand (strand 8); (iii) the register between strands 8 and 9 was shifted by three residues. Replacing the original sequence for turn 8/9 with a stronger turn motif restored the original strand register but still with a flipped beta-strand 9. The stability differences of these distinct structures were surprisingly small, consistent with an energy landscape where multiple low-energy states with different beta-sheet configurations exist. The observed conformations can be rationalized in terms of maximizing the number of backbone H-bonds. These results suggest that adjacent beta-strands "stick" through the use of factors that are not highly sequence specific and that beta-strands could slide back and forth relatively easily in the absence of external elements such as turns and tertiary packing.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antigens, Surface / chemistry*
  • Antigens, Surface / genetics
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Vaccines / chemistry*
  • Bacterial Vaccines / genetics
  • Borrelia / chemistry
  • Borrelia / genetics
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Lipoproteins / chemistry*
  • Lipoproteins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thermodynamics


  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Lipoproteins
  • OspA protein