Featured Research

from universities, journals, and other organizations

'Fishy' Clue Helps Establish How Proteins Evolve

Date:
January 29, 2009
Source:
Yale University
Summary:
Three billion years ago, a "new" amino acid was added to the alphabet of 20 that commonly make up proteins in organisms today. Now researchers have demonstrated how this rare amino acid -- and, by example, other amino acids -- made its way into the menu for protein synthesis.

This is a model of Pyl tRNA and tRNA synthetase interaction.
Credit: Marsland/Yale

Three billion years ago, a "new" amino acid was added to the alphabet of 20 that commonly make up proteins in organisms today. Now researchers at Yale and the University of Tokyo have demonstrated how this rare amino acid — and, by example, other amino acids — made its way into the menu for protein synthesis.

The rare amino acid the Yale researchers studied, pyrrolysine (Pyl), gave the researchers a molecular handle by being an extreme example of an amino acid that evolved to serve a highly specific need.

The amino acid alphabet shapes the language of proteins. When the genetic code was deciphered four decades ago, scientists believed that there were no more than 20 amino acid "letters" that universally meshed with the nucleic acid part of the protein code. But, like many alphabets, the language of proteins has letters with modifications — like accent marks — that modify their use.

When cells make proteins, a tightly coordinated pair of molecules — a tRNA and a tRNA synthetase — ensure that the correct amino acid is added in a growing protein chain. These molecules are highly specific for the amino acid they "manage" and are coded directly in the genome. All of the 20 common amino acids are incorporated into proteins in this way. However, only two uncommon amino acids, including Pyl, have been discovered that follow this pattern.

In most cases, an uncommon amino acid in proteins — like letters with accent marks — results from modification of one of the standard 20 amino acids after it has become part of the protein. Many human proteins are modified in this way, and deficiencies in these modifications are linked to myriad human diseases including cancer, neurodegeneration, and metabolic disorders.

"Pyl turns out to be special because it represents an uncommon amino acid that is incorporated during normal protein synthesis," said Yale postdoctoral fellow and lead co-author Patrick O'Donoghue. "This is the key difference that makes Pyl so interesting and valuable to molecular biologists. It opens the door to engineering the genetic code."

Pyl is so rare that it has been found in only seven organisms. Each of these microbes evolved in an unusual environmental niche and all use methylamines — the compounds that make fish smell "fishy" — as a source of energy. Söll's research team characterized and crystallized the molecules that "manage" Pyl and created images that show how these molecules have evolved to work together.

"This is the handle we needed to effectively produce an 'expanded' genetic code," said O'Donoghue. "Now we have the ability to directly genetically encode other uncommon amino acids. By doing that, we will be able to isolate the role of particular modifications and to begin to understand their functions and their role in human disease."

"We have found why it is probably not accidental that out of more than 300 amino acids found in natural proteins, only two have been added beyond the standard 20-member amino acid alphabet," said principal investigator Dieter Söll, Sterling Professor of Molecular Biophysics & Biochemistry and professor of chemistry at Yale.

"This work provides a tantalizing glimpse into how proteins have evolved in living cells," said Laurie Tompkins, who oversees protein synthesis grants at the National Institutes of Health's National Institute of General Medical Sciences, which partially supported the work. "The unique way in which the synthetase binds its tRNA substrate is a testament to the ancient roots of this remarkable enzyme."

The research was supported by grants from the National Institute of General Medical Sciences, the Department of Energy and the National Science Foundation, as well as the Japan Science and Technology Agency, the Japanese National Project on Protein Structural and Functional Analyses, the Mitsubishi Foundation, and the Kurata Memorial Hitachi Science and Technology Foundation. Patrick O'Donoghue holds a National Science Foundation postdoctoral fellowship in biological informatics.


Story Source:

The above story is based on materials provided by Yale University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nozawa et al. Pyrrolysyl-tRNA synthetase–tRNAPyl structure reveals the molecular basis of orthogonality. Nature, Dec 31, 2008; DOI: 10.1038/nature07611

Cite This Page:

Yale University. "'Fishy' Clue Helps Establish How Proteins Evolve." ScienceDaily. ScienceDaily, 29 January 2009. <www.sciencedaily.com/releases/2009/01/090127112043.htm>.
Yale University. (2009, January 29). 'Fishy' Clue Helps Establish How Proteins Evolve. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2009/01/090127112043.htm
Yale University. "'Fishy' Clue Helps Establish How Proteins Evolve." ScienceDaily. www.sciencedaily.com/releases/2009/01/090127112043.htm (accessed August 1, 2014).

Share This




More Plants & Animals News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pyrenees Orphan Bear Cub Gets Brand New Home

Pyrenees Orphan Bear Cub Gets Brand New Home

AFP (Aug. 1, 2014) — The discovery of a bear cub in the Pyrenees mountains made headlines in April 2014. Despire several attempts to find the animal's mother, the cub remained alone. Now, the Pyrenees Conservation Foundation has constructed an enclosure. Duration: 00:31 Video provided by AFP
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) — Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) — Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
Visitors Feel Part of the Pack at Wolf Preserve

Visitors Feel Part of the Pack at Wolf Preserve

AP (July 31, 2014) — Seacrest Wolf Preserve on the northern Florida panhandle allows more than 10,000 visitors each year to get up close and personal with Arctic and British Columbian Wolves. (July 31) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins