Strong Contributions from Vertical Triads to Helix-Partner Preferences in Parallel Coiled Coils

Jay D. Steinkruger, Gail J. Bartlett, Derek N. Woolfson*, Samuel H. Gellman

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

11 Citations (Scopus)

Abstract

Pairing preferences in heterodimeric coiled coils are determined by complementarities among side chains that pack against one another at the helix-helix interface. However, relationships between dimer stability and interfacial residue identity are not fully understood. In the context of the "knobs-into-holes" (KIH) packing pattern, one can identify two classes of interactions between side chains from different helices: "lateral", in which a line connecting the adjacent side chains is perpendicular to the helix axes, and "vertical", in which the connecting line is parallel to the helix axes. We have previously analyzed vertical interactions in antiparallel coiled coils and found that one type of triad constellation (a'-a-a') exerts a strong effect on pairing preferences, while the other type of triad (d'-d-d') has relatively little impact on pairing tendencies. Here, we ask whether vertical interactions (d'-a-d') influence pairing in parallel coiled-coil dimers. Our results indicate that vertical interactions can exert a substantial impact on pairing specificity, and that the influence of the d'-a-d' triad depends on the lateral a' contact within the local KIH motif. Structure-informed bioinformatic analyses of protein sequences reveal trends consistent with the thermodynamic data derived from our experimental model system in suggesting that heterotriads involving Leu and Ile are preferred over homotriads involving Leu and Ile.

Original languageEnglish
Pages (from-to)15652-15655
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number38
DOIs
Publication statusPublished - 26 Sep 2012

Structured keywords

  • Bristol BioDesign Institute

Keywords

  • DESIGN
  • SEQUENCE
  • OLIGOMERIZATION STATE
  • AMINO-ACID
  • PROTEIN
  • RESIDUES
  • STABILITY
  • POSITION
  • SPECIFICITY
  • SYNTHETIC BIOLOGY

Projects

Cite this