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. 1992 Apr;61(4):858–867. doi: 10.1016/S0006-3495(92)81893-3

Analysis of the three-alpha-helix motif in the spectrin superfamily of proteins.

D A Parry 1, T W Dixon 1, C Cohen 1
PMCID: PMC1260345  PMID: 1581500

Abstract

Members of the spectrin superfamily of proteins contain different numbers of homologous repeats arranged in tandem. Each of these consists of a three-alpha-helix motif, comprising two similarly and one oppositely directed alpha-helical segment joined by nonhelical linkers of characteristic length. The right-handed alpha-helices each display a heptad repeat in their amino acid sequences indicative of left-handed coiled-coil-like packing. We have calculated the potential number of inter-helix ionic interactions that specify the spatial arrangement of the helices in the motif in terms of both the handedness of helix connectivity (left or right) and the relative axial stagger between the three alpha-helices. All of the models examined were constrained to have optimal coiled-coil packing. For alpha-spectrin and alpha-actinin the results provide strong support for a left-handed connectivity of the three helices and axial repeat lengths of 5.05 and 6.24 nm, respectively. Furthermore, the axial staggers between homologous segments in the preferred models are identical. The insights provided into the topography of this widespread tertiary fold may prove of value to those concerned with the problem of de novo protein design.

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Selected References

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

  1. Baron M. D., Davison M. D., Jones P., Critchley D. R. The sequence of chick alpha-actinin reveals homologies to spectrin and calmodulin. J Biol Chem. 1987 Dec 25;262(36):17623–17629. [PubMed] [Google Scholar]
  2. Bowie J. U., Lüthy R., Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991 Jul 12;253(5016):164–170. doi: 10.1126/science.1853201. [DOI] [PubMed] [Google Scholar]
  3. Byers T. J., Husain-Chishti A., Dubreuil R. R., Branton D., Goldstein L. S. Sequence similarity of the amino-terminal domain of Drosophila beta spectrin to alpha actinin and dystrophin. J Cell Biol. 1989 Oct;109(4 Pt 1):1633–1641. doi: 10.1083/jcb.109.4.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen C., Parry D. A. Alpha-helical coiled coils and bundles: how to design an alpha-helical protein. Proteins. 1990;7(1):1–15. doi: 10.1002/prot.340070102. [DOI] [PubMed] [Google Scholar]
  5. Conway J. F., Parry D. A. Structural features in the heptad substructure and longer range repeats of two-stranded alpha-fibrous proteins. Int J Biol Macromol. 1990 Oct;12(5):328–334. doi: 10.1016/0141-8130(90)90023-4. [DOI] [PubMed] [Google Scholar]
  6. Cross R. A., Stewart M., Kendrick-Jones J. Structural predictions for the central domain of dystrophin. FEBS Lett. 1990 Mar 12;262(1):87–92. doi: 10.1016/0014-5793(90)80160-k. [DOI] [PubMed] [Google Scholar]
  7. Cusack S., Berthet-Colominas C., Härtlein M., Nassar N., Leberman R. A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. Nature. 1990 Sep 20;347(6290):249–255. doi: 10.1038/347249a0. [DOI] [PubMed] [Google Scholar]
  8. Davison M. D., Baron M. D., Critchley D. R., Wootton J. C. Structural analysis of homologous repeated domains in alpha-actinin and spectrin. Int J Biol Macromol. 1989 Apr;11(2):81–90. doi: 10.1016/0141-8130(89)90047-0. [DOI] [PubMed] [Google Scholar]
  9. Dubreuil R. R., Byers T. J., Sillman A. L., Bar-Zvi D., Goldstein L. S., Branton D. The complete sequence of Drosophila alpha-spectrin: conservation of structural domains between alpha-spectrins and alpha-actinin. J Cell Biol. 1989 Nov;109(5):2197–2205. doi: 10.1083/jcb.109.5.2197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koenig M., Monaco A. P., Kunkel L. M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 1988 Apr 22;53(2):219–228. doi: 10.1016/0092-8674(88)90383-2. [DOI] [PubMed] [Google Scholar]
  11. Matsudaira P. Modular organization of actin crosslinking proteins. Trends Biochem Sci. 1991 Mar;16(3):87–92. doi: 10.1016/0968-0004(91)90039-x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Noegel A., Witke W., Schleicher M. Calcium-sensitive non-muscle alpha-actinin contains EF-hand structures and highly conserved regions. FEBS Lett. 1987 Sep 14;221(2):391–396. doi: 10.1016/0014-5793(87)80962-6. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Parry D. A., Steven A. C., Steinert P. M. The coiled-coil molecules of intermediate filaments consist of two parallel chains in exact axial register. Biochem Biophys Res Commun. 1985 Mar 29;127(3):1012–1018. doi: 10.1016/s0006-291x(85)80045-0. [DOI] [PubMed] [Google Scholar]
  16. Phillips G. N., Jr, Fillers J. P., Cohen C. Tropomyosin crystal structure and muscle regulation. J Mol Biol. 1986 Nov 5;192(1):111–131. doi: 10.1016/0022-2836(86)90468-7. [DOI] [PubMed] [Google Scholar]
  17. Pons F., Augier N., Heilig R., Léger J., Mornet D., Léger J. J. Isolated dystrophin molecules as seen by electron microscopy. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7851–7855. doi: 10.1073/pnas.87.20.7851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Shotton D. M., Burke B. E., Branton D. The molecular structure of human erythrocyte spectrin. Biophysical and electron microscopic studies. J Mol Biol. 1979 Jun 25;131(2):303–329. doi: 10.1016/0022-2836(79)90078-0. [DOI] [PubMed] [Google Scholar]
  20. Speicher D. W., Marchesi V. T. Erythrocyte spectrin is comprised of many homologous triple helical segments. Nature. 1984 Sep 13;311(5982):177–180. doi: 10.1038/311177a0. [DOI] [PubMed] [Google Scholar]
  21. Wasenius V. M., Saraste M., Salvén P., Erämaa M., Holm L., Lehto V. P. Primary structure of the brain alpha-spectrin. J Cell Biol. 1989 Jan;108(1):79–93. doi: 10.1083/jcb.108.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Winograd E., Hume D., Branton D. Phasing the conformational unit of spectrin. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10788–10791. doi: 10.1073/pnas.88.23.10788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Xu Y., Prabhakaran M., Johnson M. E., Fung L. W. Secondary structure prediction for the spectrin 106-amino acid segment, and a proposed model for tertiary structure. J Biomol Struct Dyn. 1990 Aug;8(1):55–62. doi: 10.1080/07391102.1990.10507789. [DOI] [PubMed] [Google Scholar]

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