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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>