A seven-helix coiled coil

Jie Liu, Qi Zheng, Yiqun Deng, Chao Sheng Cheng, Neville R. Kallenbach, Min Lu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)15457-15462
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number42
DOIs
StatePublished - Oct 17 2006

Keywords

  • Buried polar interactions
  • Cavity
  • Helix-helix interfaces
  • Protein design
  • Protein structure

ASJC Scopus subject areas

  • General

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    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 of the United States of America, 103(42), 15457-15462. https://doi.org/10.1073/pnas.0604871103