2i5v

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(New page: 200px<br /><applet load="2i5v" size="350" color="white" frame="true" align="right" spinBox="true" caption="2i5v, resolution 1.10&Aring;" /> '''Crystal structure of...)
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==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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[[Category: de novo protein]]
[[Category: de novo protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:25:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:49:28 2008''

Revision as of 15:49, 21 February 2008


2i5v, resolution 1.10Å

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Crystal structure of OspA mutant

Overview

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.

About this Structure

2I5V is a Single protein structure of sequence from Borrelia burgdorferi with as ligand. Full crystallographic information is available from OCA.

Reference

Hydrophobic surface burial is the major stability determinant of a flat, single-layer beta-sheet., Yan S, Gawlak G, Makabe K, Tereshko V, Koide A, Koide S, J Mol Biol. 2007 Apr 20;368(1):230-43. Epub 2007 Feb 7. PMID:17335845

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