Download MendeleyA seven-helix coiled coil.
Liu, J., Zheng, Q., Deng, Y., Cheng, C.S., Kallenbach, N.R., Lu, M.(2006) Proc Natl Acad Sci U S A 103: 15457-15462
- PubMed: 17030805
- DOI: https://doi.org/10.1073/pnas.0604871103
- Primary Citation of Related Structures:
2HY6 - PubMed Abstract:
Coiled-coil proteins contain a characteristic seven-residue sequence repeat whose positions are designated a to g. The interacting surface between alpha-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 alpha-helical heptamer in aqueous solution. The 1.25-A 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 alpha-helices.
Organizational Affiliation:
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
