Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers decipher protein structure of key molecule in DNA transcription system

04.07.2011
Scientists have deciphered the structure of an essential part of Mediator, a complex molecular machine that plays a vital role in regulating the transcription of DNA.

The research adds an important link to discoveries that have enabled scientists to gain a deeper understanding of how cells translate genetic information into the proteins and processes of life. The findings, published in the July 3 advance online issue of the journal Nature, were reported by a research team led by Yuichiro Takagi, Ph.D., assistant professor of biochemistry and molecular biology at Indiana University School of Medicine.

The fundamental operations of all cells are controlled by the genetic information – the genes –stored in each cell's DNA, a long double-stranded chain. Information copied from sections of the DNA – through a process called transcription – leads to synthesis of messenger RNA, eventually enabling the production of proteins necessary for cellular function. Transcription is undertaken by the enzyme called RNA polymerase II.

As cellular operations proceed, signals are sent to the DNA asking that some genes be activated and others be shut down. The Mediator transcription regulator accepts and interprets those instructions, telling RNA polymerase II where and when to begin the transcription process.

Mediator is a gigantic molecular machine composed of 25 proteins organized into three modules known as the head, the middle, and the tail. Using X-ray crystallography, the Takagi team was able to describe in detail the structure of the Mediator Head module, the most important for interactions with RNA polymerase II.

"It's turned out to be extremely novel, revealing how a molecular machine is built from multiple proteins," said Takagi.

"As a molecular machine, the Mediator head module needs to have elements of both stability and flexibility in order to accommodate numerous interactions. A portion of the head we named the neck domain provides the stability by arranging the five proteins in a polymer-like structure," he said.

"We call it the alpha helical bundle," said Dr. Takagi. "People have seen structures of alpha helical bundles before but not coming from five different proteins."

"This is a completely noble structure," he said.

One immediate benefit of the research will be to provide detailed mapping of previously known mutations that affect the regulation of the transcription process, he said.

The ability to solve such complex structures will be important because multi-protein complexes such as Mediator will most likely become a new generation of drug targets for treatment of disease, he said.

Previously, the structure of RNA polymerase II was determined by Roger Kornberg of Stanford University, with whom Dr. Takagi worked prior to coming to IU School of Medicine. Kornberg received the Nobel Prize in 2006 for his discoveries. The researchers who described the structure of the ribosome, the protein production machine, were awarded the Nobel Prize in 2009. The structure of the entire Mediator has yet to be described, and thus remains the one of grand challenges in structure biology. Dr. Takagi's work on the Mediator head module structure represents a major step towards a structure determination of the entire Mediator.

In addition to Dr. Takagi as a senior author, the lead author for the Nature paper was Tsuyoshi Imasaki, Ph.D., of the IU School of Medicine. Other collaborators included researchers at The Scripps Research Institute, Stanford University, Memorial Sloan-Kettering Cancer Center and the European Molecular Biology Laboratory.

Funding for the research was supplied by grants from the National Science Foundation, the American Heart Association, Human Frontier Science Program, the National Institutes of Health, the National Cancer Institute and the European Commission.

Eric Schoch | EurekAlert!
Further information:
http://www.iupui.edu

Further reports about: Cancer DNA Mediator Medicine Nature Immunology Nobel Prize RNA RNA polymerase genetic information

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>