Navigation Links
How the hat fits: Structural biology study reveals shape of epigenetic enzyme complex
Date:1/20/2011

To understand the emerging science of epigeneticsa field that describes how genes may be regulated without altering the underlying DNA itselfscientists 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 lysineone 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 scaleat 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."


'/>"/>

Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert  

Related biology news :

1. Structural biology scores with protein snapshot
2. National Science Foundations awards grant to Oklahoma structural biology group
3. National Science Foundation awards grant to Oklahoma structural biology group
4. University of Nevada professor studies structural basis for autism disorders
5. Structural defects precede functional decline in heart muscle
6. Pitt/Iowa team finds cellular structural molecule can be toxic: Makes pneumonia worse
7. Structural Genomics Consortium releases 1,000th protein structure
8. Structural genomics accelerates protein structure determination
9. MRI scans show structural brain changes in people at risk for Alzheimers disease
10. Blood pressure control system found in kidneys structural units
11. Illuminating biology: An evolutionary perspective
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
How the hat fits: Structural biology study reveals shape of epigenetic enzyme complex
(Date:6/16/2016)... June 16, 2016 The ... expected to reach USD 1.83 billion by 2024, ... Research, Inc. Technological proliferation and increasing demand in ... expected to drive the market growth. ... The development of advanced multimodal techniques for ...
(Date:6/3/2016)... LONDON , June 3, 2016 /PRNewswire/ ... Transport Management) von Nepal ... ,Angebot und Lieferung hochsicherer geprägter Kennzeichen, einschließlich ... weltweit führend in der Produktion und Implementierung ... an der Ausschreibung im Januar teilgenommen, aber ...
(Date:5/24/2016)... Ampronix facilitates superior patient care by providing unparalleled technology to leaders of the medical ... premium product recently added to the range of products distributed by Ampronix. ... ... ... Ampronix News ...
Breaking Biology News(10 mins):
(Date:6/22/2016)... Research and Markets has announced the addition of the ... The global biomarkers market has ... The market is expected to grow at a five-year compound annual ... $50.6 billion in 2015 to $96.6 billion in 2020. ... to 2020) are discussed. As well, new products approved in 2013 ...
(Date:6/22/2016)... LOS ANGELES , June 22, 2016   ... an SNNLive Video Interview with Dr. Nader Pourhassan ... a biotechnology company focused on the clinical development and ... and prevention of HIV infection, according to the company,s ... was recorded on Tuesday, June 7 th , 2016, ...
(Date:6/22/2016)... DIEGO , June 22, 2016   ViaCyte, ... first pluripotent stem cell-derived islet replacement therapy for the ... presentations at ISSCR 2016 Annual Meeting.  ISSCR 2016, the ... to 25th at Moscone West in San Francisco.  ... of the presentations are as follows:Event: , Focus Session: ...
(Date:6/22/2016)... (PRWEB) , ... June 22, 2016 , ... ... at placing a spotlight on immigrant achievements and contributions to North Texas and ... most important contributors from the immigrant community to the civic and economic vitality ...
Breaking Biology Technology: