Hydrophobic surface burial is the major stability determinant of a flat, single-layer β-sheet

JOURNAL OF MOLECULAR BIOLOGY

卷:368

Article

Yan, Shude ; Gawlak, Grzegorz ; Makabe, Koki ; Tereshko, Valentina ; Koide, Akiko ; Koide, Shohei

关键词: protein folding;    energetics;    hydrophobic effect;    secondary structure propensity;    X-ray crystallography;   

DOI  :  10.1016/j.jmb.2007.02.003

来源: Elsevier

【 摘 要 】

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-scan-ning 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 nonpolar 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 -sheet layer in peptide self-assembly. (c) 2007 Elsevier Ltd. All rights reserved.

【 授权许可】

Free