No doubt the quest for the Holy Grail will continue for years, if not decades. Researchers are only beginning to design novel proteins while sitting at the keyboard. The amino acid chain remains a Rosetta stone with the wealth of information on how proteins fold largely undeciphered. Nonetheless, the empirical data that researchers have collected are beginning to yield patterns that are providing valuable clues as well as insights into the mechanisms of gene regulation, which is one of the most fundamental processes in biology. The coiled coil, says Alber, "although simple, has been especially rich. On the one hand, we are finding out how protein-protein interactions control gene expression. On the other hand, we've described a simple structural motif in enough detail that we now think we know how to design this motif. This is a small step in the direction of being able to design proteins."
Alber, T. 1992. Structure of the leucine zipper. Current Opinion in Genetics & Development 2:205–210.
Alber, T. 1993. How GCN4 binds DNA. Current Biology 3:182–184.
Brändén, C.-I., and T. A. Jones. 1990. Between objectivity and subjectivity. Nature 343:687–689.
Crick, F. H. C. 1952. Is keratin a coiled coil? Nature 170:882–884.
Crick, F. H. C. 1953. The packing of a-helices: simple coiled coils. Acta Crystallographica 6:689–697.
Harbury, P. B., T. Zhang, P. S. Kim, and T. Alber. 1993. A switch between two-, three- and four-stranded coiled coils revealed by mutants of the GCN4 leucine zipper. Science, in press.
Mattherw, B. W. 1993. Structural and genetic analysis of protein stability. Annual Review of Biochemistry 62:139–160.
McKnight, S. L. 1991. Molecular zippers in gene regulation. Scientific American 264(4):54–64.
Olson, A. J., and D. S. Goodsell. 1992. Visualizing biological molecules. Scientific American 267(5):76–81.
O'Shea, E. K., J. D. Klemm, P. S. Kim, and T. Alber. 1991. X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science 254:539–544.
Pauling, L., and R. B. Corey. 1953. Compound helical configurations of polypeptide chains: structure of proteins of the a-keratin type. Nature 171:59–61.
Richards, F. M. 1991. The protein folding problem. Scientific American 264(1):54–63.
Wüthrich, K. 1989. Protein structure determination by nuclear magnetic resonance spectroscopy. Science 243:45–50.