Towards predicting coiled-coil protein interactions

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.

[1]  P S Kim,et al.  Repacking protein cores with backbone freedom: structure prediction for coiled coils. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P. S. Kim,et al.  X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. , 1991, Science.

[3]  Vladimir N. Vapnik,et al.  The Nature of Statistical Learning Theory , 2000, Statistics for Engineering and Information Science.

[4]  James C. Hu,et al.  Sequence requirements for coiled-coils: analysis with lambda repressor-GCN4 leucine zipper fusions. , 1990, Science.

[5]  E. Wolf,et al.  A computationally directed screen identifying interacting coiled coils from Saccharomyces cerevisiae. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Eisenberg,et al.  Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Woolfson,et al.  Buried polar residues and structural specificity in the GCN4 leucine zipper , 1996, Nature Structural Biology.

[8]  Vladimir Vapnik,et al.  Statistical learning theory , 1998 .

[9]  James C. Hu,et al.  Oligomerization properties of GCN4 leucine zipper e and g position mutants , 1997, Protein science : a publication of the Protein Society.

[10]  D. Parry Coiled-coils in α-helix-containing proteins: analysis of the residue types within the heptad repeat and the use of these data in the prediction of coiled-coils in other proteins , 1982, Bioscience reports.

[11]  T. Sun,et al.  Monoclonal antibody analysis of bovine epithelial keratins. Specific pairs as defined by coexpression. , 1986, The Journal of biological chemistry.

[12]  C. Vinson,et al.  Dimerization specificity of the leucine zipper-containing bZIP motif on DNA binding: prediction and rational design. , 1993, Genes & development.

[13]  B. Berger,et al.  MultiCoil: A program for predicting two‐and three‐stranded coiled coils , 1997, Protein science : a publication of the Protein Society.

[14]  C. Vinson,et al.  Leucine is the most stabilizing aliphatic amino acid in the d position of a dimeric leucine zipper coiled coil. , 1997, Biochemistry.

[15]  James C. Hu,et al.  Probing the roles of residues at the e and g positions of the GCN4 leucine zipper by combinatorial mutagenesis , 1993, Protein science : a publication of the Protein Society.

[16]  B. Berger,et al.  Predicting coiled coils by use of pairwise residue correlations. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. S. Kim,et al.  A switch between two-, three-, and four-stranded coiled coils in GCN4 leucine zipper mutants. , 1993, Science.

[18]  B. Geiger,et al.  A subfamily of relatively large and basic cytokeratin polypeptides as defined by peptide mapping is represented by one or several polypeptides in epithelial cells. , 1982, The EMBO journal.

[19]  O. Mangasarian,et al.  Massive data discrimination via linear support vector machines , 2000 .

[20]  W. Franke,et al.  Pair formation and promiscuity of cytokeratins: formation in vitro of heterotypic complexes and intermediate-sized filaments by homologous and heterologous recombinations of purified polypeptides , 1985, The Journal of cell biology.

[21]  H. Hurst,et al.  Transcription factors. 1: bZIP proteins. , 1994, Protein profile.

[22]  F. Crick,et al.  The packing of α‐helices: simple coiled‐coils , 1953 .

[23]  P. S. Kim,et al.  High-resolution protein design with backbone freedom. , 1998, Science.

[24]  Thorsten Joachims,et al.  Making large scale SVM learning practical , 1998 .

[25]  Mona Singh,et al.  An Iterative Method for Improved Protein Structural Motif Recognition , 1997, J. Comput. Biol..

[26]  K Weber,et al.  The coiled coil of in vitro assembled keratin filaments is a heterodimer of type I and II keratins: use of site-specific mutagenesis and recombinant protein expression , 1990, The Journal of cell biology.

[27]  R Quinlan,et al.  Intermediate filament proteins. , 1995, Protein profile.

[28]  Benjamin Geiger,et al.  The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells , 1982, Cell.

[29]  A. Lupas,et al.  Predicting coiled coils from protein sequences , 1991, Science.

[30]  M Singh,et al.  Computational learning reveals coiled coil-like motifs in histidine kinase linker domains , 1998, Proc. Natl. Acad. Sci. USA.

[31]  D A Parry,et al.  Structure of alpha-keratin: structural implication of the amino acid sequences of the type I and type II chain segments. , 1977, Journal of molecular biology.

[32]  D A Parry,et al.  Structural features in the heptad substructure and longer range repeats of two-stranded alpha-fibrous proteins. , 1990, International journal of biological macromolecules.

[33]  P. S. Kim,et al.  Mechanism of specificity in the Fos-Jun oncoprotein heterodimer , 1992, Cell.

[34]  H. Bosshard,et al.  Thermodynamic characterization of the coupled folding and association of heterodimeric coiled coils (leucine zippers). , 1996, Journal of molecular biology.

[35]  C. Vinson,et al.  A thermodynamic scale for leucine zipper stability and dimerization specificity: e and g interhelical interactions. , 1994, The EMBO journal.

[36]  A. Mclachlan,et al.  Tropomyosin coiled-coil interactions: evidence for an unstaggered structure. , 1975, Journal of molecular biology.

[37]  C. Vinson,et al.  Inter-helical interactions in the leucine zipper coiled coil dimer: pH and salt dependence of coupling energy between charged amino acids. , 1998, Journal of molecular biology.

[38]  M Singh,et al.  LearnCoil-VMF: computational evidence for coiled-coil-like motifs in many viral membrane-fusion proteins , 1999, Journal of Molecular Biology.

[39]  Anton J. Enright,et al.  Protein interaction maps for complete genomes based on gene fusion events , 1999, Nature.

[40]  Tom Alber,et al.  Crystal structures of a single coiled-coil peptide in two oligomeric states reveal the basis for structural polymorphism , 1996, Nature Structural Biology.

[41]  Lumb,et al.  A buried polar interaction imparts structural uniqueness in a designed heterodimeric coiled coil , 1998, Biochemistry.

[42]  J. N. Mark Glover,et al.  Crystal structure of the heterodimeric bZIP transcription factor c-Fos–c-Jun bound to DNA , 1995, Nature.

[43]  D. Eisenberg,et al.  Detecting protein function and protein-protein interactions from genome sequences. , 1999, Science.