Inside human cells, proteins play a critical role in gene expression, yet many of these proteins lack a stable structure. Researchers at Baylor College of Medicine have discovered that certain components rely on a structured "bridge" protein to activate genes.
The study focused on "BAF complexes," which are essential for opening DNA and preparing genes for expression. Dr. H. Courtney Hodges, the senior corresponding author, explained that BAF complexes consist largely of disordered regions acting like "floppy noodles."
Published in Molecular Cell, the research reveals that these disordered parts use beta-catenin as an adapter to connect with other proteins. “Beta-catenin has a stable molecular structure that acts like a docking station,” said Hodges.
The study began by examining adrenocortical carcinoma (ACC), an adrenal cancer causing hormonal imbalances. The team aimed to understand the molecular mechanisms driving these disruptions. “We aimed to understand the root molecular mechanisms driving these hormone disruptions to find a better way to treat this disease,” said Dr. Yuen San Chan, first author of the study.
Their findings show that BAF interacts with beta-catenin directly, enabling it to locate and open genes encoding steroid enzymes. This mechanism is also relevant for other gene regulators involved in stress responses and cancer progression.
“Our findings challenge the way we think about disorder in biology,” said Dr. Katerina Cermakova, co-corresponding author at Baylor.
Collaborating institutions include MD Anderson Cancer Center and others internationally.
