A parallel coiled-coil tetramer with offset helices

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

Research output: Contribution to journalArticle

Abstract

Specific helix-helix interactions are fundamental in assembling the native state of proteins and in protein-protein interfaces. Coiled coils afford a unique model system for elucidating principles of molecular recognition between α helices. The coiled-coil fold is specified by a characteristic seven amino acid repeat containing hydrophobic residues at the first (a) and fourth (d) positions. Nonpolar side chains spaced three and four residues apart are referred to as the 3-4 hydrophobic repeat. The presence of apolar amino acids at the e or g positions (corresponding to a 3-3-1 hydrophobic repeat) can provide new possibilities for close-packing of α-helices that includes examples such as the lac repressor tetramerization domain. Here we demonstrate that an unprecedented coiled-coil interface results from replacement of three charged residues at the e positions in the dimeric GCN4 leucine zipper by nonpolar valine side chains. Equilibrium circular dichroism and analytical ultracentrifugation studies indicate that the valine-containing mutant forms a discrete α-helical tetramer with a significantly higher stability than the parent leucine-zipper molecule. The 1.35 Å resolution crystal structure of the tetramer reveals a parallel four-stranded coiled coil with a three-residue interhelical offset. The local packing geometry of the three hydrophobic positions in the tetramer conformation is completely different from that seen in classical tetrameric structures yet bears resemblance to that in three-stranded coiled coils. These studies demonstrate that distinct van der Waals interactions beyond the a and d side chains can generate a diverse set of helix-helix interfaces and three-dimensional supercoil structures.

Original languageEnglish (US)
Pages (from-to)15224-15231
Number of pages8
JournalBiochemistry
Volume45
Issue number51
DOIs
StatePublished - Dec 26 2006

Fingerprint

Leucine Zippers
Valine
Lac Repressors
Amino Acids
Molecular recognition
Proteins
Ultracentrifugation
Circular Dichroism
Conformations
Crystal structure
Molecules
Geometry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, J., Deng, Y., Zheng, Q., Cheng, C. S., Kallenbach, N. R., & Lu, M. (2006). A parallel coiled-coil tetramer with offset helices. Biochemistry, 45(51), 15224-15231. https://doi.org/10.1021/bi061914m

A parallel coiled-coil tetramer with offset helices. / Liu, Jie; Deng, Yiqun; Zheng, Qi; Cheng, Chao Sheng; Kallenbach, Neville R.; Lu, Min.

In: Biochemistry, Vol. 45, No. 51, 26.12.2006, p. 15224-15231.

Research output: Contribution to journalArticle

Liu, J, Deng, Y, Zheng, Q, Cheng, CS, Kallenbach, NR & Lu, M 2006, 'A parallel coiled-coil tetramer with offset helices', Biochemistry, vol. 45, no. 51, pp. 15224-15231. https://doi.org/10.1021/bi061914m
Liu J, Deng Y, Zheng Q, Cheng CS, Kallenbach NR, Lu M. A parallel coiled-coil tetramer with offset helices. Biochemistry. 2006 Dec 26;45(51):15224-15231. https://doi.org/10.1021/bi061914m
Liu, Jie ; Deng, Yiqun ; Zheng, Qi ; Cheng, Chao Sheng ; Kallenbach, Neville R. ; Lu, Min. / A parallel coiled-coil tetramer with offset helices. In: Biochemistry. 2006 ; Vol. 45, No. 51. pp. 15224-15231.
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