Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Dec 1;90(23):11109–11113. doi: 10.1073/pnas.90.23.11109

Dimer formation by an N-terminal coiled coil in the APC protein.

G Joslyn 1, D S Richardson 1, R White 1, T Alber 1
PMCID: PMC47931  PMID: 8248216

Abstract

Mutations in the human APC gene are associated with an inherited predisposition to colon cancer. APC codes for polypeptides of approximately 2800 amino acids, with sequence homologies to coiled-coil proteins in the first 900 residues. To determine the oligomerization properties of the APC protein, we used genetic and biochemical approaches to examine the ability of APC fragments to self-associate. A subdomain comprising the first 55 amino acids of APC was found to form a stable, parallel, helical dimer, as expected for a coiled coil. The location of a key dimerization element at the N terminus of the protein supports models in which mutations in APC exert effects through dimerization of the mutant gene products.

Full text

PDF
11109

Images in this article

11112Fig. 3
on p.11112

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. Bodmer W. F., Bailey C. J., Bodmer J., Bussey H. J., Ellis A., Gorman P., Lucibello F. C., Murday V. A., Rider S. H., Scambler P. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987 Aug 13;328(6131):614–616. doi: 10.1038/328614a0. [DOI] [PubMed] [Google Scholar]
  3. Bourne H. R. Colon cancer. Consider the coiled coil.... Nature. 1991 May 16;351(6323):188–190. doi: 10.1038/351188a0. [DOI] [PubMed] [Google Scholar]
  4. Bourne H. R. Colon cancer. Suppression with a difference. Nature. 1991 Oct 24;353(6346):696–697. doi: 10.1038/353696b0. [DOI] [PubMed] [Google Scholar]
  5. Burt R. W., Samowitz W. S. The adenomatous polyp and the hereditary polyposis syndromes. Gastroenterol Clin North Am. 1988 Dec;17(4):657–678. [PubMed] [Google Scholar]
  6. 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]
  7. Gill S. C., von Hippel P. H. Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem. 1989 Nov 1;182(2):319–326. doi: 10.1016/0003-2697(89)90602-7. [DOI] [PubMed] [Google Scholar]
  8. Groden J., Gelbert L., Thliveris A., Nelson L., Robertson M., Joslyn G., Samowitz W., Spirio L., Carlson M., Burt R. Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals. Am J Hum Genet. 1993 Feb;52(2):263–272. [PMC free article] [PubMed] [Google Scholar]
  9. Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [PubMed] [Google Scholar]
  10. Hu J. C., O'Shea E. K., Kim P. S., Sauer R. T. Sequence requirements for coiled-coils: analysis with lambda repressor-GCN4 leucine zipper fusions. Science. 1990 Dec 7;250(4986):1400–1403. doi: 10.1126/science.2147779. [DOI] [PubMed] [Google Scholar]
  11. Hunter I., Schulthess T., Engel J. Laminin chain assembly by triple and double stranded coiled-coil structures. J Biol Chem. 1992 Mar 25;267(9):6006–6011. [PubMed] [Google Scholar]
  12. KAISER A. D., JACOB F. Recombination between related temperate bacteriophages and the genetic control of immunity and prophage localization. Virology. 1957 Dec;4(3):509–521. doi: 10.1016/0042-6822(57)90083-1. [DOI] [PubMed] [Google Scholar]
  13. Kinzler K. W., Nilbert M. C., Su L. K., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hedge P., McKechnie D. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. doi: 10.1126/science.1651562. [DOI] [PubMed] [Google Scholar]
  14. Lau S. Y., Taneja A. K., Hodges R. S. Synthesis of a model protein of defined secondary and quaternary structure. Effect of chain length on the stabilization and formation of two-stranded alpha-helical coiled-coils. J Biol Chem. 1984 Nov 10;259(21):13253–13261. [PubMed] [Google Scholar]
  15. Leppert M., Dobbs M., Scambler P., O'Connell P., Nakamura Y., Stauffer D., Woodward S., Burt R., Hughes J., Gardner E. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987 Dec 4;238(4832):1411–1413. doi: 10.1126/science.3479843. [DOI] [PubMed] [Google Scholar]
  16. Lovejoy B., Choe S., Cascio D., McRorie D. K., DeGrado W. F., Eisenberg D. Crystal structure of a synthetic triple-stranded alpha-helical bundle. Science. 1993 Feb 26;259(5099):1288–1293. doi: 10.1126/science.8446897. [DOI] [PubMed] [Google Scholar]
  17. Miyoshi Y., Ando H., Nagase H., Nishisho I., Horii A., Miki Y., Mori T., Utsunomiya J., Baba S., Petersen G. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4452–4456. doi: 10.1073/pnas.89.10.4452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665–669. doi: 10.1126/science.1651563. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. O'Shea E. K., Rutkowski R., Kim P. S. Evidence that the leucine zipper is a coiled coil. Science. 1989 Jan 27;243(4890):538–542. doi: 10.1126/science.2911757. [DOI] [PubMed] [Google Scholar]
  21. O'Shea E. K., Rutkowski R., Stafford W. F., 3rd, Kim P. S. Preferential heterodimer formation by isolated leucine zippers from fos and jun. Science. 1989 Aug 11;245(4918):646–648. doi: 10.1126/science.2503872. [DOI] [PubMed] [Google Scholar]
  22. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  23. Smith K. J., Johnson K. A., Bryan T. M., Hill D. E., Markowitz S., Willson J. K., Paraskeva C., Petersen G. M., Hamilton S. R., Vogelstein B. The APC gene product in normal and tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846–2850. doi: 10.1073/pnas.90.7.2846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Spirio L., Otterud B., Stauffer D., Lynch H., Lynch P., Watson P., Lanspa S., Smyrk T., Cavalieri J., Howard L. Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus. Am J Hum Genet. 1992 Jul;51(1):92–100. [PMC free article] [PubMed] [Google Scholar]
  25. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  26. Su L. K., Johnson K. A., Smith K. J., Hill D. E., Vogelstein B., Kinzler K. W. Association between wild type and mutant APC gene products. Cancer Res. 1993 Jun 15;53(12):2728–2731. [PubMed] [Google Scholar]
  27. Zhou N. E., Kay C. M., Hodges R. S. Synthetic model proteins: the relative contribution of leucine residues at the nonequivalent positions of the 3-4 hydrophobic repeat to the stability of the two-stranded alpha-helical coiled-coil. Biochemistry. 1992 Jun 30;31(25):5739–5746. doi: 10.1021/bi00140a008. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES