Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1995 Nov;4(11):2252–2260. doi: 10.1002/pro.5560041102

The Alacoil: a very tight, antiparallel coiled-coil of helices.

K M Gernert 1, M C Surles 1, T H Labean 1, J S Richardson 1, D C Richardson 1
PMCID: PMC2143020  PMID: 8563621

Abstract

The Alacoil is an antiparallel (rather than the usual parallel) coiled-coil of alpha-helices with Ala or another small residue in every seventh position, allowing a very close spacing of the helices (7.5-8.5 A between local helix axes), often over four or five helical turns. It occurs in two distinct types that differ by which position of the heptad repeat is occupied by Ala and by whether the closest points on the backbone of the two helices are aligned or are offset by half a turn. The aligned, or ROP, type has Ala in position "d" of the heptad repeat, which occupies the "tip-to-tip" side of the helix contact where the C alpha-C beta bonds point toward each other. The more common offset, or ferritin, type of Alacoli has Ala in position "a" of the heptad repeat (where the C alpha-C beta bonds lie back-to-back, on the "knuckle-touch" side of the helix contact), and the backbones of the two helices are offset vertically by half a turn. In both forms, successive layers of contact have the Ala first on one and then on the other helix. The Alacoil structure has much in common with the coiled-coils of fibrous proteins or leucine zippers: both are alpha-helical coiled-coils, with a critical amino acid repeated every seven residues (the Leu or the Ala) and a secondary contact position in between. However, Leu zippers are between aligned, parallel helices (often identical, in dimers), whereas Alacoils are between antiparallel helices, usually offset, and much closer together. The Alacoil, then, could be considered as an "Ala anti-zipper." Leu zippers have a classic "knobs-into-holes" packing of the Leu side chain into a diamond of four residues on the opposite helix; for Alacoils, the helices are so close together that the Ala methyl group must choose one side of the diamond and pack inside a triangle of residues on the other helix. We have used the ferritin-type Alacoil as the basis for the de novo design of a 66-residue, coiled helix hairpin called "Alacoilin." Its sequence is: cmSPDQWDKE AAQYDAHAQE FEKKSHRNng TPEADQYRHM ASQY QAMAQK LKAIANQLKK Gsetcr (with "a" heptad positions underlined and nonhelical parts in lowercase), which we will produce and test for both stability and uniqueness of structure.

Full Text

The Full Text of this article is available as a PDF (4.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banner D. W., Kokkinidis M., Tsernoglou D. Structure of the ColE1 rop protein at 1.7 A resolution. J Mol Biol. 1987 Aug 5;196(3):657–675. doi: 10.1016/0022-2836(87)90039-8. [DOI] [PubMed] [Google Scholar]
  2. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  3. Chothia C. Principles that determine the structure of proteins. Annu Rev Biochem. 1984;53:537–572. doi: 10.1146/annurev.bi.53.070184.002541. [DOI] [PubMed] [Google Scholar]
  4. Chou P. Y., Fasman G. D. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. doi: 10.1146/annurev.bi.47.070178.001343. [DOI] [PubMed] [Google Scholar]
  5. DeGrado W. F., Wasserman Z. R., Lear J. D. Protein design, a minimalist approach. Science. 1989 Feb 3;243(4891):622–628. doi: 10.1126/science.2464850. [DOI] [PubMed] [Google Scholar]
  6. Efimov A. V. Packing of alpha-helices in globular proteins. Layer-structure of globin hydrophobic cores. J Mol Biol. 1979 Oct 15;134(1):23–40. doi: 10.1016/0022-2836(79)90412-1. [DOI] [PubMed] [Google Scholar]
  7. Fedorov A. N., Dolgikh D. A., Chemeris V. V., Chernov B. K., Finkelstein A. V., Schulga A. A., Alakhov YuB, Kirpichnikov M. P., Ptitsyn O. B. De novo design, synthesis and study of albebetin, a polypeptide with a predetermined three-dimensional structure. Probing the structure at the nanogram level. J Mol Biol. 1992 Jun 20;225(4):927–931. doi: 10.1016/0022-2836(92)90092-x. [DOI] [PubMed] [Google Scholar]
  8. Fezoui Y., Weaver D. L., Osterhout J. J. De novo design and structural characterization of an alpha-helical hairpin peptide: a model system for the study of protein folding intermediates. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3675–3679. doi: 10.1073/pnas.91.9.3675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  10. Harper E. T., Rose G. D. Helix stop signals in proteins and peptides: the capping box. Biochemistry. 1993 Aug 3;32(30):7605–7609. doi: 10.1021/bi00081a001. [DOI] [PubMed] [Google Scholar]
  11. Hecht M. H., Richardson J. S., Richardson D. C., Ogden R. C. De novo design, expression, and characterization of Felix: a four-helix bundle protein of native-like sequence. Science. 1990 Aug 24;249(4971):884–891. doi: 10.1126/science.2392678. [DOI] [PubMed] [Google Scholar]
  12. Hill C. P., Anderson D. H., Wesson L., DeGrado W. F., Eisenberg D. Crystal structure of alpha 1: implications for protein design. Science. 1990 Aug 3;249(4968):543–546. doi: 10.1126/science.2382133. [DOI] [PubMed] [Google Scholar]
  13. Hodges R. S., Saund A. K., Chong P. C., St-Pierre S. A., Reid R. E. Synthetic model for two-stranded alpha-helical coiled-coils. Design, synthesis, and characterization of an 86-residue analog of tropomyosin. J Biol Chem. 1981 Feb 10;256(3):1214–1224. [PubMed] [Google Scholar]
  14. Kamtekar S., Schiffer J. M., Xiong H., Babik J. M., Hecht M. H. Protein design by binary patterning of polar and nonpolar amino acids. Science. 1993 Dec 10;262(5140):1680–1685. doi: 10.1126/science.8259512. [DOI] [PubMed] [Google Scholar]
  15. Klingler T. M., Brutlag D. L. Discovering structural correlations in alpha-helices. Protein Sci. 1994 Oct;3(10):1847–1857. doi: 10.1002/pro.5560031024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuroda Y., Nakai T., Ohkubo T. Solution structure of a de novo helical protein by 2D-NMR spectroscopy. J Mol Biol. 1994 Feb 25;236(3):862–868. doi: 10.1006/jmbi.1994.1194. [DOI] [PubMed] [Google Scholar]
  17. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  18. Lawson D. M., Artymiuk P. J., Yewdall S. J., Smith J. M., Livingstone J. C., Treffry A., Luzzago A., Levi S., Arosio P., Cesareni G. Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature. 1991 Feb 7;349(6309):541–544. doi: 10.1038/349541a0. [DOI] [PubMed] [Google Scholar]
  19. McLachlan A. D., Stewart M. Tropomyosin coiled-coil interactions: evidence for an unstaggered structure. J Mol Biol. 1975 Oct 25;98(2):293–304. doi: 10.1016/s0022-2836(75)80119-7. [DOI] [PubMed] [Google Scholar]
  20. Munson M., O'Brien R., Sturtevant J. M., Regan L. Redesigning the hydrophobic core of a four-helix-bundle protein. Protein Sci. 1994 Nov;3(11):2015–2022. doi: 10.1002/pro.5560031114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. O'Shea E. K., Klemm J. D., Kim P. S., Alber T. X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science. 1991 Oct 25;254(5031):539–544. doi: 10.1126/science.1948029. [DOI] [PubMed] [Google Scholar]
  22. Ptitsyn O. B., Pain R. H., Semisotnov G. V., Zerovnik E., Razgulyaev O. I. Evidence for a molten globule state as a general intermediate in protein folding. FEBS Lett. 1990 Mar 12;262(1):20–24. doi: 10.1016/0014-5793(90)80143-7. [DOI] [PubMed] [Google Scholar]
  23. Quinn T. P., Tweedy N. B., Williams R. W., Richardson J. S., Richardson D. C. Betadoublet: de novo design, synthesis, and characterization of a beta-sandwich protein. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8747–8751. doi: 10.1073/pnas.91.19.8747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Richards F. M., Kundrot C. E. Identification of structural motifs from protein coordinate data: secondary structure and first-level supersecondary structure. Proteins. 1988;3(2):71–84. doi: 10.1002/prot.340030202. [DOI] [PubMed] [Google Scholar]
  25. Richardson D. C., Richardson J. S. Kinemages--simple macromolecular graphics for interactive teaching and publication. Trends Biochem Sci. 1994 Mar;19(3):135–138. doi: 10.1016/0968-0004(94)90207-0. [DOI] [PubMed] [Google Scholar]
  26. Richardson D. C., Richardson J. S. The kinemage: a tool for scientific communication. Protein Sci. 1992 Jan;1(1):3–9. doi: 10.1002/pro.5560010102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Richardson J. S., Richardson D. C. Amino acid preferences for specific locations at the ends of alpha helices. Science. 1988 Jun 17;240(4859):1648–1652. doi: 10.1126/science.3381086. [DOI] [PubMed] [Google Scholar]
  28. Richardson J. S., Richardson D. C., Tweedy N. B., Gernert K. M., Quinn T. P., Hecht M. H., Erickson B. W., Yan Y., McClain R. D., Donlan M. E. Looking at proteins: representations, folding, packing, and design. Biophysical Society National Lecture, 1992. Biophys J. 1992 Nov;63(5):1185–1209. [PMC free article] [PubMed] [Google Scholar]
  29. Richardson J. S. The anatomy and taxonomy of protein structure. Adv Protein Chem. 1981;34:167–339. doi: 10.1016/s0065-3233(08)60520-3. [DOI] [PubMed] [Google Scholar]
  30. Richmond T. J., Richards F. M. Packing of alpha-helices: geometrical constraints and contact areas. J Mol Biol. 1978 Mar 15;119(4):537–555. doi: 10.1016/0022-2836(78)90201-2. [DOI] [PubMed] [Google Scholar]
  31. Robertson D. E., Farid R. S., Moser C. C., Urbauer J. L., Mulholland S. E., Pidikiti R., Lear J. D., Wand A. J., DeGrado W. F., Dutton P. L. Design and synthesis of multi-haem proteins. Nature. 1994 Mar 31;368(6470):425–432. doi: 10.1038/368425a0. [DOI] [PubMed] [Google Scholar]
  32. Seale J. W., Srinivasan R., Rose G. D. Sequence determinants of the capping box, a stabilizing motif at the N-termini of alpha-helices. Protein Sci. 1994 Oct;3(10):1741–1745. doi: 10.1002/pro.5560031014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Smith T. F., Waterman M. S. Identification of common molecular subsequences. J Mol Biol. 1981 Mar 25;147(1):195–197. doi: 10.1016/0022-2836(81)90087-5. [DOI] [PubMed] [Google Scholar]
  34. Surles M. C., Richardson J. S., Richardson D. C., Brooks F. P., Jr Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling system. Protein Sci. 1994 Feb;3(2):198–210. doi: 10.1002/pro.5560030205. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES