Studies highlight the role of chaotic protein interactions in gene expression

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A team led by researchers at Baylor College of Medicine and the Czech Academy of Sciences has discovered a new piece of the puzzle of how gene expression is regulated.Published in the journal ChemistryThe findings reveal new mechanisms that regulate the assembly of intracellular components that control gene expression. This mechanism is not only essential for normal cell function, but is also involved in cancer, neurodegeneration, and HIV infection, and may suggest new ways to treat these conditions.

“Most research to date has focused on specific cellular components. gene Dr. H. Courtney Hodges, an assistant professor of molecular and cell biology and co-author of Baylor’s Center for Precision Environmental Health, said: The rate of gene expression can also function collectively to fine-tune expression levels in many different settings. We have put these proteins together and identified a mechanism that plays a broad role in health and disease. “

In a previous study with a colleague from KU Leuven in Belgium, the team studied protein interactions in leukemia and HIV infection, especially those mediated by a protein region called the TFIIS N-terminal domain (TND). In current research, researchers have extended their work on TND and found them in many other proteins.

“Everywhere we look, these domains are found in mechanisms that regulate transcriptional elongation, which is one of the first steps in gene expression, especially in all human cells. Transcriptional elongation is found in many different proteins. It’s a complex cellular process that works together. ” Lead author Dr. Katerina Selmakova, postdoctoral fellow in Hodges Lab. “We found that TND is the most concentrated structural element of all transcriptional elongation factors. Looking for them, all important protein complexes involved in transcriptional elongation have TND or TND. You can see that it is bound to a protein with. “

Previous studies have suggested to researchers that TND functions like a docking platform for other protein regions, especially a small portion of unstructured proteins known as TND interaction motifs (TIMs).

Proteins have segments with well-organized 3D structures, but many proteins also have segments that lack such organization. These chaotic or unstructured areas often work.

“One of the notable points of these unstructured areas is their anomalous behavior as a molecule,” said a structural biologist and group leader at the Institute of Organic Chemistry and Biochemistry at the Czech Academy of Sciences (IOCB Prague). One co-author, Dr. Vaclav Veverka, said: “Imagine a TIM as a string that moves as if it were loosened at one end and blown off by a hurricane. But when you find a TND partner, the string is rounded and firmly fixed to the TND and kept close. Researchers have shown that this attachment plays an important role in the early stages of gene expression.

“First, we confirmed that TND and TIM were bound in a’test tube’type experiment, but we confirmed that they were bound to each other in living cells, and the association of observations in biological systems. Verifying sex was very exciting, “Cermakova said. “We also determined that the TND-TIM interaction was very specific.”

Hodges, a member of Baylor’s Dan L Duncan Comprehensive Cancer Center, said:

“IWS1 uses specific TND-TIM interactions to regulate the activity of many transcription factors at the same time, discovering that all elements appear to be symphonic conductors that continue to function in harmony and close together. We did, “said Veverka.

The team also investigated the consequences of disrupting a single unstructured protein region. Transcription elongation To process.

“Destroying even one unstructured region changed hundreds of genes with important functions,” Hodges said. “The first step in gene expression has begun, but it paused and could not be completed, hindering efficient gene expression.”

This study highlights the undervalued role of disorder protein Interaction as the main orchestrator of Gene expression And other complex biological functions. Findings can also contribute to a better understanding of diseases such as cancer and viral infections, Neurodevelopmental disorders And other conditions where these factors can collapse. TND and TIM have the potential to be important new targets for improving the treatment of these conditions.

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For more information:
Katerina Cermakova et al, a ubiquitous, disordered protein-interaction module that regulates transcriptional elongation, Chemistry (2021). DOI: 10.1126 / science.abe2913..

Quote: The study was conducted on gene expression obtained on November 25, 2021 from https: // (2021, November 25). Emphasizes the role of chaotic protein interactions in

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Studies highlight the role of chaotic protein interactions in gene expression

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