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A parallel coiled-coil tetramer with offset helices.
Biochemistry. 2006 Dec 26; 45(51):15224-31.B

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 alpha 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 alpha-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 alpha-helical tetramer with a significantly higher stability than the parent leucine-zipper molecule. The 1.35 A 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.

Authors+Show Affiliations

Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17176044

Citation

Liu, Jie, et al. "A Parallel Coiled-coil Tetramer With Offset Helices." Biochemistry, vol. 45, no. 51, 2006, pp. 15224-31.
Liu J, Deng Y, Zheng Q, et al. A parallel coiled-coil tetramer with offset helices. Biochemistry. 2006;45(51):15224-31.
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), 15224-31.
Liu J, et al. A Parallel Coiled-coil Tetramer With Offset Helices. Biochemistry. 2006 Dec 26;45(51):15224-31. PubMed PMID: 17176044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A parallel coiled-coil tetramer with offset helices. AU - Liu,Jie, AU - Deng,Yiqun, AU - Zheng,Qi, AU - Cheng,Chao-Sheng, AU - Kallenbach,Neville R, AU - Lu,Min, Y1 - 2006/11/29/ PY - 2006/12/21/pubmed PY - 2008/1/12/medline PY - 2006/12/21/entrez SP - 15224 EP - 31 JF - Biochemistry JO - Biochemistry VL - 45 IS - 51 N2 - 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 alpha 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 alpha-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 alpha-helical tetramer with a significantly higher stability than the parent leucine-zipper molecule. The 1.35 A 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. SN - 1520-4995 UR - https://www.unboundmedicine.com/medline/citation/17176044/A_parallel_coiled_coil_tetramer_with_offset_helices_ L2 - https://doi.org/10.1021/bi061914m DB - PRIME DP - Unbound Medicine ER -