Conformational Transition between Four and Five-stranded Phenylalanine Zippers Determined by a Local Packing Interaction

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

Research output: Contribution to journalArticlepeer-review


Alpha-helical coiled coils play a crucial role in mediating specific protein-protein interactions. However, the rules and mechanisms that govern helix-helix association in coiled coils remain incompletely understood. Here we have engineered a seven heptad "Phe-zipper" protein (Phe-14) with phenylalanine residues at all 14 hydrophobic a and d positions, and generated a further variant (Phe-14M) in which a single core Phe residue is substituted with Met. Phe-14 forms a discrete α-helical pentamer in aqueous solution, while Phe-14M folds into a tetrameric helical structure. X-ray crystal structures reveal that in both the tetramer and the pentamer the a and d side-chains interlock in a classical knobs-into-holes packing to produce parallel coiled-coil structures enclosing large tubular cavities. However, the presence of the Met residue in the apolar interface of the tetramer markedly alters its local coiled-coil conformation and superhelical geometry. Thus, short-range interactions involving the Met side-chain serve to preferentially select for tetramer formation, either by inhibiting a nucleation step essential for pentamer folding or by abrogating an intermediate required to form the pentamer. Although specific trigger sequences have not been clearly identified in dimeric coiled coils, higher-order coiled coils, as well as other oligomeric multi-protein complexes, may require such sequences to nucleate and direct their assembly.

Original languageEnglish (US)
Pages (from-to)168-179
Number of pages12
JournalJournal of Molecular Biology
Issue number1
StatePublished - Aug 4 2006


  • coiled coils
  • protein engineering
  • protein folding
  • protein structure

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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