Towards predicting coiled-coil protein interactions

ABSTRACT

Protein-protein interactions play a central role in many cellular functions, and as whole-genome data accumulates, computational methods for predicting these interactions become increasingly important. Computational methods have already proven to be a useful first step for rapid genome-wide identification of putative protein structure and function, but research on the problem of computationally determining biologically relevant partners for given protein sequences is just beginning. In this paper, we approach the problem of predicting protein-protein interactions by focusing on the 2- stranded coiled-coil motif. We introduce a computational method for predicting coiled-coil protein interactions, and give a novel framework that is able to use both genomic sequence data and experimental data in making these predictions. Cross-validation tests show that the method is able to predict many aspects of protein-protein interactions mediated by the coiled-coil motif, and suggest that this methodology can be used as the basis for genome-wide prediction of coiled-coil protein interactions.

REFERENCES

• 1: B. Berger and M. Singh. An iterative method for improved protein structural motif recognition, or. Computational Biol., 4(3):261-273, 1997.
• 2: B. Berger, D. B. Wilson, E. Wolf, T. Tonchev, M. Milla, and P. S. Kim. Predicting coiled coils using pairwise residue correlations. Proc. Natl. Acad. Sci. USA, 92:8259-8263, 1995.
• 3: B. Bradley and O. Mangasarian. Massive data discrimination via linear support vector machines. Optimization Methods and Software, 13(1):1-10, 2000.
• 4: Christopher J. C. Burges, A Tutorial on Support Vector Machines for Pattern Recognition, Data Mining and Knowledge Discovery, v.2 n.2, p.121-167, June 1998 [doi>10.1023/A:1009715923555 ]
• 5: J. Conway and D. Parry. Structural features in the heptad substructure and longer range repeats of two-stranded-fibrous proteins. International Journal of Biological Macromolecules, 12:328-333, October 1990.
• 6: D. Cooper and T.-T. Sun. Monoclonal antibody analysis of bovine epithelial keratins. Journal of Biological Chemistry, 261:4646-4654, 1986.
• 7: F. H. C. Crick. The packing of helices: simple coiled coils. Acta Cryst., 6:689-697, 1953.
• 8: A. Enright, I. Iliopoulos, N. Kyrpides, and C. Ouzounis. Protein interaction maps for complete genomes based on gene fusion events. Nature, 402:86-90, 1999.
• 9: J. Glover and S. Harrison. Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature, 373:257-261, 1995.
• 10: L. Gonzalez, R. Brown, D. Richardson, and T. Alber. Crystal structures of a single coiled-coil peptide in two oligomeric states reveal the basis for structural polymorphism. Nat. Struct. Biol., 3(12):1002-1009, 1996.
• 11: L. Gonzalez, D. Woolfson, and T. Alber. Buried polar residues and structural specificity in the GCN4 leucine zipper. Nat. Struct. Biol., 3(12):1011-1018, 1996.
• 12: P. B. Harbury, J. J. Plecs, B. Tidor, T. Alber, and P. S. Kim. High-resolution protein design with backbone freedom. Science, 282:1462-1467, 1998.
• 13: P. B. Harbury, B. Tidor, and P. S. Kim. Predicting protein cores with backbone freedom: Structure prediction for coiled coils. Proc. Natl. Acad. Sci. USA, 92:8408-8412, 1995.
• 14: P. B. Harbury, T. Zhang, P. S. Kim, and T. Alber. A switch between two-, three- and four-stranded coiled coils in GCN4 leucine zipper mutants. Science, 262:1401-1407, November 1993.
• 15: M. Hatzfeld and W. Franke. Pair formation and promiscuity of cytokeratins: Formation in vitro of heterotypic complexes and intermediate-sized filaments by homologous and heterologous recombinations of purified peptides. Journal of Cell Biology, 101:1826-1841, 1985.
• 16: M. Hatzfeld and K. Weber. The coiled coil of in vitro assembled keratin filaments is a heterodimer of type I and type II keratins: Use of site-specific mutagenesis and recombinant protein expression. J Cell Biol., 110:1199-1210, 1990.
• 17: J. Hu, N. Newell, B. Tidor, and R. Sauer. Probing the roles of residues at the e and g positions of the GCN4 leucine zipper by combinatorial mutagenesis. Protein Science, 2:1072-1084, 1993.
• 18: J. Hu, E. O'Shea, P. S. Kim, and R. Sauer. Sequence requirements for coiled coils: Analysis with lambda repressor-GCN4 leucine zipper fusions. Science, 250:1400-1403, 1990.
• 19: H. Hurst. Transcription factors 1: bzip proteins. Protein Profile, 2(2):101-168, 1995.
• 20: I. Jelesarov and H. R. Bosshard. Thermodynamic characterization of the coupled folding and association of heterodimeric coiled coils (leucine zippers). J. Mol. Biol., 263:344-358, 1996.
• 21: Thorsten Joachims, Making large-scale support vector machine learning practical, Advances in kernel methods: support vector learning, MIT Press, Cambridge, MA, 1999
• 22: D. Krylov, J. Barchi, and C. Vinson. Inter-helical interactions in the leucine zipper coiled coil dimer: pH and salt dependence of coupling energy between charged amino acids. J. Mol. Bio., 279:959-972, 1998.
• 23: D. Krylov, I. Mikhailenko, and C. Vinson. A thermodynamic scale for leucine zipper stability and dimerization specificity: e and g interhelical interactions. The EMBO journal, 13(12):2849-2861, 1994.
• 24: K. Lumb and P. S. Kim. A buried polar interaction imparts structural uniqueness in a designed heterodimeric coiled coil. Biochemistry, 34:8642-8648, 1995.
• 25: A. Lupas, M. van Dyke, and J. Stock. Predicting coiled coils from protein sequences. Science, 252:1162-1164, 1991.
• 26: E. Marcotte, M. Pellegrini, H. Ng, D. Rice, T. Yeates, and D. Eisenberg. Detecting protein function and protein-protein interactions from genome sequences. Science, 285:751-753, 1999.
• 27: A. McLachlan and M. Stewart. Tropomyosin coiled-coil interactions: Evidence for an unstaggered structure. J. Mol. Biol., 98:293-304, 1975.
• 28: J. Moitra, L. Szilak, D. Krylov, and C. Vinson. Leucine is the most stabilizing aliphatic amino acid in the d position of a dimeric leucine zipper coiled coil. Biochemistry, 36:12567-12573, 1997.
• 29: R. Moll, W. Franke, D. Schiller, B. Geiger, and R. Krepler. The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cell. Cell, 31:11-24, November 1982.
• 30: J. R. Newman, E. Wolf, and P. S. Kim. A computationally directed screen identifying interactin coiled coils from Saccharomyces cerevisiae. Proc. Nati Acad. Sci. USA, 97(24):13203-13208, 2000.
• 31: E. O'Shea, J. Klemm, P. S. Kim, and T. Alber. X-ray structure of the GCN4 leucine zipper, a two-stranded parallel coiled coil. Science, 254:539-544, October 1991.
• 32: E. O'Shea, R. Rutkowski, and P. S. Kim. Mechanism of specificity in the fos-jun oncoprotein heterodimer. Cell, 68:699-708, 1992.
• 33: D. A. D. Parry. Sequences of c-keratin: Structural implication of the amino acid sequences of the type I and type II chain segments. J. Mol. Biol, 113:449-454 1977.
• 34: D. A. D. Parry. Coiled coils in alpha-helix-containing proteins: analysis of residue types within the heptad repeat and the use of these data in the prediction of coiled-coils in other proteins. Bioscience Rep., 2:1017-1024, 1982.
• 35: M. Pellegrini, E. Marcotte, M. Thompson, D. Eisenberg, and T. Yeates. Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc. Natl. Acad. Sci. USA, 96(8) :4285-4288, 1999.
• 36: R. Quinlan, C. Hutchison, and B. Lane. Intermediate filament proteins. Protein Profile, 2(8):795-952, 1995.
• 37: D. Schiller, W. Franke, and B. Geiger. A subfamily oJ relatively large and basic cytokeratin polypeptides as defined by peptide mapping is represented by one or several polypeptides in epithelial cells. The EMBO Journal, 6:761-769, 1982.
• 38: M. Singh, B. Berger, and P. S. Kim. Learncoil-VMF: Computational evidence for coiled-coil-like motifs in many viral membrane-fusion proteins. J. Mol. Biol, 290:1031-1044, 1999.
• 39: M. Singh, B. Berger, P. S. Kim, J. Berger, and A. Cochran. Computational learning reveals coiled coil-like motifs in histidine kinase linker domains. Proc. Natl. Acad. Sci. USA, 95:2738-2743, March 1998.
• 40: Vladimir N. Vapnik, The nature of statistical learning theory, Springer-Verlag New York, Inc., New York, NY, 1995
• 41: C. Vinson, T. Hai, and S. Boyd. Dimerization specificy of the leucine zipper-containing bzip motif o DNA binding: prediction and rational design. Genes Dev., 7(6):1047-1058, 1993.
• 42: E. Wolf, P. S. Kim, and B. Berger. Multicoil: A program for predicting two- and three-stranded coilec coils. Protein Sci., 6:1179-1189, 1997.
• 43: X. Zeng, H. Zhu, H. Lashuel, and J. Hu. Oligomerization properties of GCN4 leucine zipper e and g mutants. Protein Science, 6:2218-2226, 1997.

INDEX TERMS

Primary Classification:
  J. Computer Applications
  J.3 LIFE AND MEDICAL SCIENCES
      Subjects: Biology and genetics

General Terms:
Design, Experimentation, Human Factors, Measurement, Performance, Reliability, Theory