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. 1995 Sep;4(9):1851–1859. doi: 10.1002/pro.5560040920

Evidence from sequence information that the interleukin-1 receptor is a transmembrane GTPase.

T P Hopp 1
PMCID: PMC2143205  PMID: 8528083

Abstract

Evidence is presented that the cytoplasmic domain of the type I interleukin-1 receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic amino acids that suggest a structural relatedness to the ras protooncogene protein and other members of the GTPase superfamily, despite a lack of significant detectable sequence homology. When the hydrophobic segments of the IL-1R were aligned with similar segments of the GTPases, it became apparent that the IL-1Rs possess a number of conserved amino acids that represent plausible functional residues for base-specific binding of GTP, magnesium chelation, and phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues were found that is identical between ras and the IL-1R, and which is positioned to form part of the guanine base binding pocket. If this model is correct, then the IL-1Rs possess a highly conserved effector protein binding region, but one that is entirely unrelated to the effector regions of other superfamily members. Therefore, if the IL-1R is indeed a GTPase, then its activation function may be directed to as-yet unrecognized effector target proteins, as part of a unique cellular signal transduction pathway.

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Selected References

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  1. Amor J. C., Harrison D. H., Kahn R. A., Ringe D. Structure of the human ADP-ribosylation factor 1 complexed with GDP. Nature. 1994 Dec 15;372(6507):704–708. doi: 10.1038/372704a0. [DOI] [PubMed] [Google Scholar]
  2. Bursten S. L., Harris W. E. Interleukin-1 stimulates phosphatidic acid-mediated phospholipase D activity in human mesangial cells. Am J Physiol. 1994 Apr;266(4 Pt 1):C1093–C1104. doi: 10.1152/ajpcell.1994.266.4.C1093. [DOI] [PubMed] [Google Scholar]
  3. Carpén O., Pallai P., Staunton D. E., Springer T. A. Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and alpha-actinin. J Cell Biol. 1992 Sep;118(5):1223–1234. doi: 10.1083/jcb.118.5.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  5. Cohen L., Mohr R., Chen Y. Y., Huang M., Kato R., Dorin D., Tamanoi F., Goga A., Afar D., Rosenberg N. Transcriptional activation of a ras-like gene (kir) by oncogenic tyrosine kinases. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12448–12452. doi: 10.1073/pnas.91.26.12448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Curtis B. M., Gallis B., Overell R. W., McMahan C. J., DeRoos P., Ireland R., Eisenman J., Dower S. K., Sims J. E. T-cell interleukin 1 receptor cDNA expressed in Chinese hamster ovary cells regulates functional responses to interleukin 1. Proc Natl Acad Sci U S A. 1989 May;86(9):3045–3049. doi: 10.1073/pnas.86.9.3045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Grandori R., Carey J. Six new candidate members of the alpha/beta twisted open-sheet family detected by sequence similarity to flavodoxin. Protein Sci. 1994 Dec;3(12):2185–2193. doi: 10.1002/pro.5560031204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hopp T. P. Protein surface analysis. Methods for identifying antigenic determinants and other interaction sites. J Immunol Methods. 1986 Apr 3;88(1):1–18. doi: 10.1016/0022-1759(86)90045-1. [DOI] [PubMed] [Google Scholar]
  10. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hultmark D. Macrophage differentiation marker MyD88 is a member of the Toll/IL-1 receptor family. Biochem Biophys Res Commun. 1994 Feb 28;199(1):144–146. doi: 10.1006/bbrc.1994.1206. [DOI] [PubMed] [Google Scholar]
  12. Lambright D. G., Noel J. P., Hamm H. E., Sigler P. B. Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature. 1994 Jun 23;369(6482):621–628. doi: 10.1038/369621a0. [DOI] [PubMed] [Google Scholar]
  13. Lee J. O., Rieu P., Arnaout M. A., Liddington R. Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). Cell. 1995 Feb 24;80(4):631–638. doi: 10.1016/0092-8674(95)90517-0. [DOI] [PubMed] [Google Scholar]
  14. Letourneau P. C., Shattuck T. A. Distribution and possible interactions of actin-associated proteins and cell adhesion molecules of nerve growth cones. Development. 1989 Mar;105(3):505–519. doi: 10.1242/dev.105.3.505. [DOI] [PubMed] [Google Scholar]
  15. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  16. Mishima K., Tsuchiya M., Nightingale M. S., Moss J., Vaughan M. ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP-ribosylation factor domain. J Biol Chem. 1993 Apr 25;268(12):8801–8807. [PubMed] [Google Scholar]
  17. Mizel S. B. How does interleukin 1 activate cells? Cyclic AMP and interleukin 1 signal transduction. Immunol Today. 1990 Nov;11(11):390–391. doi: 10.1016/0167-5699(90)90154-2. [DOI] [PubMed] [Google Scholar]
  18. Muegge K., Williams T. M., Kant J., Karin M., Chiu R., Schmidt A., Siebenlist U., Young H. A., Durum S. K. Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1. Science. 1989 Oct 13;246(4927):249–251. doi: 10.1126/science.2799385. [DOI] [PubMed] [Google Scholar]
  19. Nakashima H., Nishikawa K., Ooi T. The folding type of a protein is relevant to the amino acid composition. J Biochem. 1986 Jan;99(1):153–162. doi: 10.1093/oxfordjournals.jbchem.a135454. [DOI] [PubMed] [Google Scholar]
  20. Pollerberg G. E., Burridge K., Krebs K. E., Goodman S. R., Schachner M. The 180-kD component of the neural cell adhesion molecule N-CAM is involved in cell-cell contacts and cytoskeleton-membrane interactions. Cell Tissue Res. 1987 Oct;250(1):227–236. doi: 10.1007/BF00214676. [DOI] [PubMed] [Google Scholar]
  21. Saklatvala J., Bird T. A., Kaur P., O'Neill L. A. IL-1 signal transduction: evidence of activation of G protein and protein kinase. Prog Clin Biol Res. 1990;349:285–295. [PubMed] [Google Scholar]
  22. Schäcke H., Müller W. E., Gamulin V., Rinkevich B. The Ig superfamily includes members from the lowest invertebrates to the highest vertebrates. Immunol Today. 1994 Oct;15(10):497–498. doi: 10.1016/0167-5699(94)90198-8. [DOI] [PubMed] [Google Scholar]
  23. Sewell J. L., Kahn R. A. Sequences of the bovine and yeast ADP-ribosylation factor and comparison to other GTP-binding proteins. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4620–4624. doi: 10.1073/pnas.85.13.4620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shirakawa F., Mizel S. B. In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol Cell Biol. 1989 Jun;9(6):2424–2430. doi: 10.1128/mcb.9.6.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sondek J., Lambright D. G., Noel J. P., Hamm H. E., Sigler P. B. GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4. Nature. 1994 Nov 17;372(6503):276–279. doi: 10.1038/372276a0. [DOI] [PubMed] [Google Scholar]
  26. Takio K., Wade R. D., Smith S. B., Krebs E. G., Walsh K. A., Titani K. Guanosine cyclic 3',5'-phosphate dependent protein kinase, a chimeric protein homologous with two separate protein families. Biochemistry. 1984 Aug 28;23(18):4207–4218. doi: 10.1021/bi00313a030. [DOI] [PubMed] [Google Scholar]
  27. Weng G., Chen C. X., Balogh-Nair V., Callender R., Manor D. Hydrogen bond interactions of G proteins with the guanine ring moiety of guanine nucleotides. Protein Sci. 1994 Jan;3(1):22–29. doi: 10.1002/pro.5560030104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]

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