2I5Z

The crystal structure of OspA mutant

Summary for 2I5Z

• Entry DOI: 10.2210/pdb2i5z/pdb
• Descriptor: Outer surface protein A, TETRAETHYLENE GLYCOL (3 entities in total)
• Functional Keywords: beta-sheet, de novo protein
• Biological source: Borrelia burgdorferi (Lyme disease spirochete)
• Total number of polymer chains: 1
• Total formula weight: 26571.63

Authors

Makabe, K.,Terechko, V.,Koide, S. (deposition date: 2006-08-26, release date: 2007-07-10, Last modification date: 2023-08-30)

Primary citation

Yan, S.,Gawlak, G.,Makabe, K.,Tereshko, V.,Koide, A.,Koide, S.
Hydrophobic surface burial is the major stability determinant of a flat, single-layer beta-sheet.
J.Mol.Biol., 368:230-243, 2007

PubMed Abstract: Formation of a flat beta-sheet is a fundamental event in beta-sheet-mediated protein self-assembly. To investigate the contributions of various factors to the stability of flat beta-sheets, we performed extensive alanine-scanning mutagenesis experiments on the single-layer beta-sheet segment of Borrelia outer surface protein A (OspA). This beta-sheet segment consists of beta-strands with highly regular geometries that can serve as a building block for self-assembly. Our Ala-scanning approach is distinct from the conventional host-guest method, in that it introduces only conservative, truncation mutations that should minimize structural perturbation. Our results showed very weak correlation with experimental beta-sheet propensity scales, statistical beta-sheet propensity scales, or cross-strand pairwise correlations. In contrast, our data showed strong positive correlation with the change in buried non-polar surface area. Polar interactions including prominent Glu-Lys cross-strand pairs contribute marginally to the beta-sheet stability. These results were corroborated by results from additional non-Ala mutations. Taken together, these results demonstrate the dominant contribution of non-polar surface burial to flat beta-sheet stability even at solvent-exposed positions. The OspA single-layer beta-sheet achieves efficient hydrophobic surface burial without forming a hydrophobic core by a strategic placement of a variety of side-chains. These findings further suggest the importance of hydrophobic interactions within a beta-sheet layer in peptide self-assembly.

PubMed: 17335845
DOI: 10.1016/j.jmb.2007.02.003

Experimental method

X-RAY DIFFRACTION (1.2 Å)