Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How the hat fits: Structural biology study reveals shape of epigenetic enzyme complex

21.01.2011
Acetylation complex fits like a halo over a histone

To understand the emerging science of epigenetics—a field that describes how genes may be regulated without altering the underlying DNA itself—scientists are deciphering the many ways in which enzymes act on the proteins surrounding DNA within cells.

One type of these enzymes, proteins known as histone acetyltransferases (HATs), act on DNA by modifying DNA-bound proteins called histones. This act of modification, called acetlyation, can dictate how histones interact with DNA and other proteins affecting processes such as DNA replication, transcription (reading the gene), and repair. In the February 9 issue of the journal Structure, available online, researchers at The Wistar Institute are the first to describe the complete atomic structure formed by a yeast HAT, known as Rtt109, and one of its associated proteins. Their findings demonstrate how a particular histone acetylation event works, a crucial step to understanding epigenetics and the related processes that underlie both health and disease.

According to the study's senior author, Ronen Marmorstein, Ph.D., professor and program leader of Wistar's Gene Expression and Regulation Program, two copies of Rtt109 bind to two copies of a "chaperone" protein to form a ring.

"The ring fits atop a histone much like a halo, and we find that the type of chaperone dictates exactly how the enzyme affects the histone by determining the exact position of acetylation," said Marmorstein. "The structure represents a nice model system for the regulation of protein acetylation, and teaches us something new about the biology of this enzyme, Rtt109."

The act of acetylation adds an "acetyl group," a small chemical structure, to a lysine—one of the amino acids that make up a given protein. Altering one lysine could change the shape of a protein, such as a histone, in a subtle way, perhaps redirecting how it functions. Rtt109, the researchers say, acetylates any of three specific lysines on histones, and exactly which of the histone lysines are modified is determined by which chaperone escorts Rtt109 into place. Since histones are such crucial DNA-associated proteins, altering a single lysine in a single part of the structure can have profound effects on the "behavior" of that histone, such as exposing a particular set of genes to be read, for example.

In the paper, Marmorstein and his colleagues show how Rtt109 associates with a particular chaperone called Vps75. Rtt109 also associates with another chaperone, Asf1, which has been shown to enable the Rtt109 to modify lysines in a different spot on a given histone, creating a different effect in how that histone interacts with DNA and in turn changing the cell's biological properties.

Their study is the first to show that two Rtt109 enzymes pair up with two Vps75 chaperones to form a ring. The laboratory created crystals of the protein complex and used a technique called X-ray crystallography to "see" the structure of the complex by analyzing the patterns formed when X-rays bounce off the crystals. They used the powerful X-ray source at the Argonne National Laboratory's Advanced Photon Source, which enabled the team to determine the structure of the protein complex at the atomic scale—at a resolution of 2.8 angstroms (2.8 billionths of a meter), which is smaller than the distance between individual rungs on the DNA ladder.

Since the Marmorstein laboratory began its work on HATs over a decade ago, several large-scale studies have shown that acetylation occurs to over 2000 proteins, not just histones. According to Marmorstein, it appears there is an entire web of communication going on within cells directly attributable to protein acetylation, another level of complexity in an already-complex field.

"We have seen many different proteins over several different pathways become affected by acetylation, which can alter the processes of RNA metabolism, cell cycle control, cancer, and a number of different aspects of life. It looks like protein acetylation has much broader biological implications than initially appreciated," said Marmorstein.

"In many ways, it seems a lot like what we have seen in recent years with protein kinases and cell signaling," said Marmorstein. "What we're learning is that these HATs, and possibly other protein acetyltransferases, are regulated in much the same way. They have these profound effects within cells, but it is still very new to science. How it works is a big black box that we intend to decipher."

This work from the Marmorstein laboratory was supported by a grant from the National Institute of General Medical Sciences.

The lead author of the study is Yong Tang, Ph.D., a staff scientist in the Marmorstein laboratory. Wistar co-authors also include Katrina Meeth, a research associate and Hua Yuan, Ph.D., a postdoctoral fellow in the Marmorstein laboratory. Collaborators include Philip A. Cole, Ph.D., and his laboratory at the Johns Hopkins University School of Medicine, including Marc A. Holbert, Ph.D.; and the laboratories of Alain Verreault, Ph.D., and Pierre Thibault, Ph.D., at the Institute for Research in Immunology and Cancer at the Université de Montréal; and their colleagues, including research associates, Neda Delgoshaie, Paul Drogaris, Chantal Durette, and Eun-Hye Lee, and postdoctoral fellows Hugo Wurtele, Ph.D., and Benoit Guillemette, Ph.D.

Greg Lester | EurekAlert!
Further information:
http://www.wistar.org

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>