Helix capping in the GCN4 leucine zipper

Min Lu, Wei Shu, Hong Ji, Erik Spek, Leyu Wang, Neville R. Kallenbach

Research output: Contribution to journalArticle

Abstract

Capping interactions associated with specific sequences at or near the ends of α-helices are important determinants of the stability of protein secondary and tertiary structure. We investigate here the role of the helix-capping motif Ser-X-X-Glu, a sequence that occurs frequently at the N termini of a helices in proteins, on the conformation and stability of the GCN4 leucine zipper. The 1.8 Å resolution crystal structure of the capped molecule reveals distinct conformations, packing geometries and hydrogen-bonding networks at the amino terminus of the two helices in the leucine zipper dimer. The free energy of helix stabilization associated with the hydrogen-bonding and hydrophobic interactions in this capping is -1.2 kcal/mol, evaluated from thermal unfolding experiments. A single cap thus contributes appreciably to stabilizing the terminated helix and thereby the native state. These results suggest that helix capping plays a further role in protein folding, providing a sensitive connector linking α-helix formation to the developing tertiary structure of a protein.

Original languageEnglish (US)
Pages (from-to)743-752
Number of pages10
JournalJournal of Molecular Biology
Volume288
Issue number4
DOIs
StatePublished - May 14 1999

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Leucine Zippers
Hydrogen Bonding
Tertiary Protein Structure
Secondary Protein Structure
Protein Conformation
Protein Stability
Protein Folding
Hydrophobic and Hydrophilic Interactions
Hot Temperature

Keywords

  • Coiled coil
  • GCN4 leucine zipper
  • Helix capping
  • Protein folding
  • Thermal stability

ASJC Scopus subject areas

  • Virology

Cite this

Lu, M., Shu, W., Ji, H., Spek, E., Wang, L., & Kallenbach, N. R. (1999). Helix capping in the GCN4 leucine zipper. Journal of Molecular Biology, 288(4), 743-752. https://doi.org/10.1006/jmbi.1999.2707

Helix capping in the GCN4 leucine zipper. / Lu, Min; Shu, Wei; Ji, Hong; Spek, Erik; Wang, Leyu; Kallenbach, Neville R.

In: Journal of Molecular Biology, Vol. 288, No. 4, 14.05.1999, p. 743-752.

Research output: Contribution to journalArticle

Lu, M, Shu, W, Ji, H, Spek, E, Wang, L & Kallenbach, NR 1999, 'Helix capping in the GCN4 leucine zipper', Journal of Molecular Biology, vol. 288, no. 4, pp. 743-752. https://doi.org/10.1006/jmbi.1999.2707
Lu M, Shu W, Ji H, Spek E, Wang L, Kallenbach NR. Helix capping in the GCN4 leucine zipper. Journal of Molecular Biology. 1999 May 14;288(4):743-752. https://doi.org/10.1006/jmbi.1999.2707
Lu, Min ; Shu, Wei ; Ji, Hong ; Spek, Erik ; Wang, Leyu ; Kallenbach, Neville R. / Helix capping in the GCN4 leucine zipper. In: Journal of Molecular Biology. 1999 ; Vol. 288, No. 4. pp. 743-752.
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N2 - Capping interactions associated with specific sequences at or near the ends of α-helices are important determinants of the stability of protein secondary and tertiary structure. We investigate here the role of the helix-capping motif Ser-X-X-Glu, a sequence that occurs frequently at the N termini of a helices in proteins, on the conformation and stability of the GCN4 leucine zipper. The 1.8 Å resolution crystal structure of the capped molecule reveals distinct conformations, packing geometries and hydrogen-bonding networks at the amino terminus of the two helices in the leucine zipper dimer. The free energy of helix stabilization associated with the hydrogen-bonding and hydrophobic interactions in this capping is -1.2 kcal/mol, evaluated from thermal unfolding experiments. A single cap thus contributes appreciably to stabilizing the terminated helix and thereby the native state. These results suggest that helix capping plays a further role in protein folding, providing a sensitive connector linking α-helix formation to the developing tertiary structure of a protein.

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