How the important TOPLESS Plant Protein Interacts with other molecules responsible for Turning Genes Off

The tetrameric TOPLESS complex with the EAR motif peptides bound at its repressor-peptide binding grooves. The repressor peptides are shown as a ball presentation. Credit: Karsten Melcher, Ph.D., Van Andel Research Institute

Scientists at Van Andel Research Institute (VARI) have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer. In plants as in animals and humans, intricate molecular networks regulate key biological functions, such as development and stress responses. When the wrong switches are flipped, genes can be inappropriately turned on or off, leading to the onset of diseases.

“This is really a fundamental discovery – our structure shows the corepressor TOPLESS interacting with key repressor motifs, which constitutes a major component of gene silencing in plants,” said Van Andel Research Institute’s Karsten Melcher, Ph.D “Understanding this interaction in plants gives us unique insight into similar pathways in humans that involve these proteins, which are notoriously tough to investigate.”

METHOD: Using Xray crystallography, the team determined the 3D structure of TOPLESS, both on its own and when linked with other molecules responsible for turning genes off, thereby regulating gene expression. Although these interacting molecules were chosen from different signaling pathways in plants, they all linked up with TOPLESS in the same manner

Although the new study provides further insight into human molecular pathways, the work also describes how components of the molecular switchboard in plants interact to regulate responses to a multitude of stressors, including temperature fluctuations.

NOTE: TOPLESS functions as a co-repressor and interacts with repressors containing ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motifs, the most common form of transcriptional repression motifs found in plants, thought to facilitate stable epigenetic regulation of gene expression via recruitment of chromatin modifiers. TOPLESS plays important roles in plant development; its name stems from the fact that mutations in TOPLESS can give rise to seedlings in which the shoot is transformed into a 2nd root, ie “topless” seedlings.
In humans, similar proteins also are altered in many types of tumors, and control embryonic development and development of neurons. http://www.vai.org/home/NewsRoom/press-release-7-24-15