High-resolution structures of a heterochiral coiled coil

David E. Mortenson, Jay D. Steinkruger, Dale F. Kreitler, Dominic V. Perroni, Gregory P. Sorenson, Lijun Huang, Ritesh Mittal, Hyun Gi Yun, Benjamin R. Travis, Mahesh K. Mahanthappa, Katrina T. Forest, Samuel H. Gellman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from D amino acids (D peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious protein- protein interactions. Coiled-coil interactions, between or among á-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled-coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between L- and D-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.

Original languageEnglish (US)
Pages (from-to)13144-13149
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number43
DOIs
StatePublished - Oct 27 2015

Keywords

  • Coiled coil
  • D peptides
  • Racemic crystallization
  • Racemic detergent
  • Transmembrane peptides

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