The enormously diverse complexity seen amongst individual species within the animal kingdom evolved from a surprisingly small gene pool. For example, mice effectively serve as medical research models because humans and mice share 80-percent of the same protein-coding genes. The key to morphological and behavioral complexity, a growing body of scientific evidence suggests, is the regulation of gene expression by a family of DNA-binding proteins called "transcription factors." Now, a team of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley has discovered the secret behind how one these critical transcription factors is able to perform a split personality.
Using a technique called single-particle cryo-electron microscopy, the team, which was led by biophysicist Eva Nogales, showed that the transcription factor known as "TFIID" can co-exist in two distinct structural states. These two states the canonical and the rearranged - differ only in the translocation of a single substructural element known as lobe A - by 100 angstroms (an atom of hydrogen is about one angstrom in diameter). This structural shift enables initiation of the transcription process by which the genetic message of DNA is copied to RNA for the eventual production of proteins.
"TFIID by itself fluctuates between the canonical and rearranged states," Nogales says. "When TFIID becomes bound to another transcription factor, TFIIA, it shifts mostly to the canonical state, but in the presence of both TFIIA and DNA, the TFIID shifts to the rearranged state, which enables recognition and binding to key DNA sequences and marks the start of the transcriptional process."
Understanding the reorganization of TFIID and its role in transcription provides new insight into the regulation of gene expression, Nogales says, a process critical to the growth, development, health and sur
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory