Skip to content

Navigating the Structural Landscape of De Novo α-Helical Bundles

Research output: Contribution to journalArticle

Standard

Navigating the Structural Landscape of De Novo α-Helical Bundles. / Rhys, Guto G; Wood, Christopher W; Beesley, Joseph L; Zaccai, Nathan R; Burton, Antony J; Brady, R Leo; Thomson, Andrew R; Woolfson, Derek N.

In: Journal of the American Chemical Society, Vol. 141, No. 22, 05.06.2019, p. 8787-8797.

Research output: Contribution to journalArticle

Harvard

Rhys, GG, Wood, CW, Beesley, JL, Zaccai, NR, Burton, AJ, Brady, RL, Thomson, AR & Woolfson, DN 2019, 'Navigating the Structural Landscape of De Novo α-Helical Bundles', Journal of the American Chemical Society, vol. 141, no. 22, pp. 8787-8797. https://doi.org/10.1021/jacs.8b13354

APA

Rhys, G. G., Wood, C. W., Beesley, J. L., Zaccai, N. R., Burton, A. J., Brady, R. L., ... Woolfson, D. N. (2019). Navigating the Structural Landscape of De Novo α-Helical Bundles. Journal of the American Chemical Society, 141(22), 8787-8797. https://doi.org/10.1021/jacs.8b13354

Vancouver

Rhys GG, Wood CW, Beesley JL, Zaccai NR, Burton AJ, Brady RL et al. Navigating the Structural Landscape of De Novo α-Helical Bundles. Journal of the American Chemical Society. 2019 Jun 5;141(22):8787-8797. https://doi.org/10.1021/jacs.8b13354

Author

Rhys, Guto G ; Wood, Christopher W ; Beesley, Joseph L ; Zaccai, Nathan R ; Burton, Antony J ; Brady, R Leo ; Thomson, Andrew R ; Woolfson, Derek N. / Navigating the Structural Landscape of De Novo α-Helical Bundles. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 22. pp. 8787-8797.

Bibtex

@article{11ef0084c5244d838525164f0fe7bbfd,
title = "Navigating the Structural Landscape of De Novo α-Helical Bundles",
abstract = "The association of amphipathic α helices in water leads to α-helical-bundle protein structures. However, the driving force for this-the hydrophobic effect-is not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increasingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundle-the α-helical coiled coils-relationships have been established that discriminate between all-parallel dimers, trimers, and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less well understood. Here, we describe a synthetic-peptide system that switches between parallel hexamers and various up-down-up-down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of α-helical coiled coils above the dimers and trimers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology.",
keywords = "SYNTHETIC BIOLOGY",
author = "Rhys, {Guto G} and Wood, {Christopher W} and Beesley, {Joseph L} and Zaccai, {Nathan R} and Burton, {Antony J} and Brady, {R Leo} and Thomson, {Andrew R} and Woolfson, {Derek N}",
year = "2019",
month = "6",
day = "5",
doi = "10.1021/jacs.8b13354",
language = "English",
volume = "141",
pages = "8787--8797",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "22",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Navigating the Structural Landscape of De Novo α-Helical Bundles

AU - Rhys, Guto G

AU - Wood, Christopher W

AU - Beesley, Joseph L

AU - Zaccai, Nathan R

AU - Burton, Antony J

AU - Brady, R Leo

AU - Thomson, Andrew R

AU - Woolfson, Derek N

PY - 2019/6/5

Y1 - 2019/6/5

N2 - The association of amphipathic α helices in water leads to α-helical-bundle protein structures. However, the driving force for this-the hydrophobic effect-is not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increasingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundle-the α-helical coiled coils-relationships have been established that discriminate between all-parallel dimers, trimers, and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less well understood. Here, we describe a synthetic-peptide system that switches between parallel hexamers and various up-down-up-down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of α-helical coiled coils above the dimers and trimers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology.

AB - The association of amphipathic α helices in water leads to α-helical-bundle protein structures. However, the driving force for this-the hydrophobic effect-is not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increasingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundle-the α-helical coiled coils-relationships have been established that discriminate between all-parallel dimers, trimers, and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less well understood. Here, we describe a synthetic-peptide system that switches between parallel hexamers and various up-down-up-down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of α-helical coiled coils above the dimers and trimers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology.

KW - SYNTHETIC BIOLOGY

UR - http://www.scopus.com/inward/record.url?scp=85066869375&partnerID=8YFLogxK

U2 - 10.1021/jacs.8b13354

DO - 10.1021/jacs.8b13354

M3 - Article

VL - 141

SP - 8787

EP - 8797

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 22

ER -