DOI: 10.1073/pnas.0604871103. A seven-helix coiled coil

10.1073/pnas.0604871103

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Coiled-coil proteins contain a characteristic seven-residue sequence repeat whose positions are designated a to g. The interacting surface between α-helices in a classical coiled coil is formed by interspersing nonpolar side chains at the a and d positions with hydrophilic residues at the flanking e and g positions. To explore how the chemical nature of these core amino acids dictates the overall coiled-coil architecture, we replaced all eight e and g residues in the GCN4 leucine zipper with nonpolar alanine side chains. Surprisingly, the alanine-containing mutant forms a stable α-helical heptamer in aqueous solution. The 1.25-Å resolution crystal structure of the heptamer reveals a parallel seven-stranded coiled coil enclosing a large tubular channel with an unusual heptad register shift between adjacent staggered helices. The overall geometry comprises two interleaved hydrophobic helical screws of interacting cross-sectional a and d layers that have not been seen before. Moreover, asparagines at the a positions play an essential role in heptamer formation by participating in a set of buried interhelix hydrogen bonds. These results demonstrate that heptad repeats containing four hydrophobic positions can direct assembly of complex, higher-order coiled-coil structures with rich diversity for close packing of α-helices.

Bibliography

Liu, J., Zheng, Q., Deng, Y., Cheng, C.-S., Kallenbach, N. R., & Lu, M. (2006). A seven-helix coiled coil. Proceedings of the National Academy of Sciences, 103(42), 15457â15462.

Authors 6

Jie Liu (first)
Qi Zheng (additional)
Yiqun Deng (additional)
Chao-Sheng Cheng (additional)
Neville R. Kallenbach (additional)
Min Lu (additional)

References 52 Referenced 206

Dates

Type	When
Created	18 years, 10 months ago (Oct. 9, 2006, 9:02 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 3:50 p.m.)
Indexed	3 weeks, 4 days ago (Aug. 6, 2025, 9:11 a.m.)
Issued	18 years, 10 months ago (Oct. 17, 2006)
Published	18 years, 10 months ago (Oct. 17, 2006)
Published Online	18 years, 10 months ago (Oct. 17, 2006)
Published Print	18 years, 10 months ago (Oct. 17, 2006)

Funders 0

None

BibTeX

@article{Liu_2006, title={A seven-helix coiled coil}, volume={103}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0604871103}, DOI={10.1073/pnas.0604871103}, number={42}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Liu, Jie and Zheng, Qi and Deng, Yiqun and Cheng, Chao-Sheng and Kallenbach, Neville R. and Lu, Min}, year={2006}, month=oct, pages={15457–15462} }

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  "abstract": "<jats:p>Coiled-coil proteins contain a characteristic seven-residue sequence repeat whose positions are designated a to g. The interacting surface between \u03b1-helices in a classical coiled coil is formed by interspersing nonpolar side chains at the a and d positions with hydrophilic residues at the flanking e and g positions. To explore how the chemical nature of these core amino acids dictates the overall coiled-coil architecture, we replaced all eight e and g residues in the GCN4 leucine zipper with nonpolar alanine side chains. Surprisingly, the alanine-containing mutant forms a stable \u03b1-helical heptamer in aqueous solution. The 1.25-\u00c5 resolution crystal structure of the heptamer reveals a parallel seven-stranded coiled coil enclosing a large tubular channel with an unusual heptad register shift between adjacent staggered helices. The overall geometry comprises two interleaved hydrophobic helical screws of interacting cross-sectional a and d layers that have not been seen before. Moreover, asparagines at the a positions play an essential role in heptamer formation by participating in a set of buried interhelix hydrogen bonds. These results demonstrate that heptad repeats containing four hydrophobic positions can direct assembly of complex, higher-order coiled-coil structures with rich diversity for close packing of \u03b1-helices.</jats:p>",
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