On Faculty: Biological Clues Folded Into Ancient Proteins Emil Venere ------------------------------------- Homewood News and Information Biophysicists are homing in on a fundamental fold of protein--essential for a multitude of life processes--that apparently has been handed down from the beginning of life on Earth. Without this ancient three-dimensional fold of protein material, DNA could not organize into chromosomes, and life as we know it would not exist. But the discovery has even broader implications; the architecture of this structure is the common element in many critical proteins, enabling the assembly and, ultimately, the functioning of various proteins crucial for life, said Evangelos Moudrianakis, one of the biophysicists involved in the work. Scientists call the structure the "histone fold," a specific three-dimensional arrangement of 65 amino acids, the building blocks of all proteins. In nature, there are many types of histones, and when they are compared to each other they appear diverse. As the Hopkins scientists found, however, each histone contains the histone fold, but its location varies from histone to histone. When they are lined up by their histone-fold regions, they appear strikingly similar. A scientific paper on the discovery was written by Gina Arents, a research associate in the Hopkins Biology Department, and Moudrianakis, a biology professor. The findings were reported in the Nov. 21 issue of Proceedings of the National Academy of Sciences. The scientists discovered another important characteristic of the histone fold: When its two halves are analyzed separately, one appears to be a duplicate of the other, and the researchers suggest that the present-day histone fold may be produced by a gene that has been duplicated from a primordial gene half its size. That means scientists now can study the biological features of an ancient element of genetic structure presumably present since the emergence of life. In their paper, the researchers described the structural characteristics of the histone fold and analyzed its possible evolutionary patterns. "It is impressive that this protein folding motif has remained essentially unchanged from the most primitive forms of life to humans," said Moudrianakis. It is found in all cellular organisms, from the simplest bacteria, to fungi and the higher plants and animals. The Hopkins scientists compared a large number of proteins, which, based on their amino acid sequences, appear unrelated. But, by using the histone fold as a new "ruler," the scientists found that the proteins are, in fact, related, and are members of a distinct protein "superfamily." The members of the family have different biological functions but appear to have evolved from a common and simple protein ancestor, the histone fold. An earlier, related study was initiated by the Hopkins scientists, along with former graduate student Andreas D. Baxevanis, who is now at the National Institutes of Health. Those earlier findings used computers to search all known proteins. The search identified the histone fold's presence in a large number of proteins that were previously considered unrelated to histones. They included enzymes and "transcription factors," proteins needed for genetic information to be expressed, and subsequently used to produce other proteins essential for cells to function. In 1991 the biologists discovered the histone fold inside a bundle of proteins, called histones, which form spools around which DNA winds itself to make chromosomes. Without the spools, DNA could not fit inside a cell's nucleus. The DNA from one human cell, if stretched straight, would be about 7 feet long. In life, however, it is bound tight and "compacted" enough to fit inside the nucleus of each of the body's trillions of cells. Each histone spool is made up of eight protein chains, organized in what is called a core histone octamer. The histone fold appears to be one of the most ancient protein structures known today and has been preserved throughout millions of years of evolution. It is found in a diverse range of proteins, and the discovery paves the way for many new findings about its function.
Go to Gazette Homepage