 |
|
Lost in translation
January 08, 2009Perfectionist protein-maker trashes errors
The enzyme machine that translates a cell's DNA code into the proteins of life is nothing if not an editorial perfectionist.
Johns Hopkins researchers, reporting this week in Nature, have discovered a new "proofreading step" during which the suite of translational tools called the ribosome recognizes errors, just after making them, and definitively responds by hitting its version of a "delete" button.
It turns out, the Johns Hopkins researchers say, that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life.
"What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress, end of story," says Rachel Green, a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics in the Johns Hopkins University School of Medicine. "There's no second chance." Previously, Green says, molecular biologists thought the ribosome tightly managed its actions only prior to the actual incorporation of the next building block by being super-selective about which chemical ingredients it allows to enter the process.
Because a protein's chemical "shape" dictates its function, mistakes in translating assembly codes can be toxic to cells, resulting in the misfolding of proteins often associated with neurodegenerative conditions. Working with bacterial ribosomes, Green and her team watched them react to lab-induced chemical errors and were surprised to see that the protein-manufacturing process didn't proceed as usual, getting past the error and continuing its "walk" along the DNA's protein-encoding genetic messages.
"We thought that once the mistake was made, it would have just gone on to make the next bond and the next," Green says. "But instead, we noticed that one mistake on the ribosomal assembly line begets another, and it's this compounding of errors that leads to the partially finished protein being tossed into the cellular trash," she adds.
To their further surprise, the ribosome lets go of error-laden proteins 10,000 times faster than it would normally release error-free proteins, a rate of destruction that Green says is "shocking" and reveals just how much of a stickler the ribosome is about high-fidelity protein synthesis.
"These are not subtle numbers," she says, noting that there's a clear biological cost for this ribosomal editing and jettisoning of errors, but a necessary expense.
"The cell is a wasteful system in that it makes something and then says, forget it, throw it out," Green concedes. "But it's evidently worth the waste to increase fidelity. There are places in life where fidelity matters."
Johns Hopkins Medical Institutions
It turns out, the Johns Hopkins researchers say, that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life.
"What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress, end of story," says Rachel Green, a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics in the Johns Hopkins University School of Medicine. "There's no second chance." Previously, Green says, molecular biologists thought the ribosome tightly managed its actions only prior to the actual incorporation of the next building block by being super-selective about which chemical ingredients it allows to enter the process.
Because a protein's chemical "shape" dictates its function, mistakes in translating assembly codes can be toxic to cells, resulting in the misfolding of proteins often associated with neurodegenerative conditions. Working with bacterial ribosomes, Green and her team watched them react to lab-induced chemical errors and were surprised to see that the protein-manufacturing process didn't proceed as usual, getting past the error and continuing its "walk" along the DNA's protein-encoding genetic messages.
"We thought that once the mistake was made, it would have just gone on to make the next bond and the next," Green says. "But instead, we noticed that one mistake on the ribosomal assembly line begets another, and it's this compounding of errors that leads to the partially finished protein being tossed into the cellular trash," she adds.
To their further surprise, the ribosome lets go of error-laden proteins 10,000 times faster than it would normally release error-free proteins, a rate of destruction that Green says is "shocking" and reveals just how much of a stickler the ribosome is about high-fidelity protein synthesis.
"These are not subtle numbers," she says, noting that there's a clear biological cost for this ribosomal editing and jettisoning of errors, but a necessary expense.
"The cell is a wasteful system in that it makes something and then says, forget it, throw it out," Green concedes. "But it's evidently worth the waste to increase fidelity. There are places in life where fidelity matters."
Johns Hopkins Medical Institutions
Ribosome Current Events and Ribosome News RSS2-pronged protein attack could be source of SARS virulence
Ever since the previously unknown SARS virus emerged from southern China in 2003, University of Texas Medical Branch at Galveston virologists have focused on finding the source of the pathogen's virulence - its ability to cause disease.
Scientists visualize assembly line gears in ribosomes, cell's protein factory
Even as research on the ribosome, one of the cell's most basic machines, is recognized with a Nobel Prize, scientists continue to achieve new insights on the way ribosomes work.
National Science Foundation congratulates Nobel Laureates in medicine/physiology, chemistry and economics
The National Science Foundation (NSF) congratulates the 2009 Nobel laureates, particularly those who have received NSF funding over the years: Jack W. Szostak, who shared the prize in physiology or medicine; Thomas A. Steitz, who shared the prize in chemistry; and Elinor Ostrom and Oliver E. Williamson who earned the Sveriges Riksbank Prize in economic sciences in memory of Alfred Nobel 2009.
What are the characteristics of clarithromycin-resistant Helicobacter pylori?
Clarithromycin is currently one of the antibiotics used for eradication of Helicobacter pylori. However, reports of H. pylori resistance to this antibiotic are increasing worldwide.
Scripps research scientists observe human neurodegenerative disorder in fruit flies
A team of scientists from The Scripps Research Institute, Katholeike Universiteit Leuven, and the University of Antwerp, Belgium, among other institutions, has created a genetically modified fruit fly that mimics key features of Charcot-Marie-Tooth disease, a common neurodegenerative disorder that strikes about one out of every 2,500 people in the United States.
NIST researchers 'all aglow' over new test of toxin strength
A new National Institute of Standards and Technology (NIST) assay using a "glow or no glow" technique may soon help the U.S. Department of Homeland Security (DHS) defend the nation against a spectrum of biological weapons that could be used in a terrorist attack.
Genetic switch potential key to new class of antibiotics
Researchers have determined the structure of a key genetic mechanism at work in bacteria, including some that are deadly to humans, in an important step toward the design of a new class of antibiotics.
Researchers study signaling networks that set up genetic code
In a new study, researchers at the University of Illinois have identified and visualized the signaling pathways in protein-RNA complexes that help set the genetic code in all organisms.
Mutations within a conservative region of HCV affects the therapy
At least 200 million individuals are currently infected with hepatitis C virus (HCV) worldwide. Approximately 30%-50% of patients respond to interferon/ribavirin combination therapy.
Researchers identify genes for thiostrepton, a powerful drug whose use is now limited
Researchers at the Georgia Institute of Technology have identified the genetic machinery responsible for synthesizing thiostrepton, a powerful antibiotic produced by certain bacteria. Though effective against the dangerous MRSA (methicillin-resistant Staphylococcus aureus) and vancomycin-resistant enterococci, thiostrepton currently has only limited applications in humans because it is not water soluble.
More Ribosome Current Events and Ribosome News Articles
 |
The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions b |
 |
Protein Synthesis and Ribosome Structure: Translating the Genome by Knud H. Nierhaus (Editor), Daniel N. Wilson (Editor) Based on more than 30 years of ribosome research and incorporating the most recent structural evidence, this book presents a uniform picture of the largest enzyme complex found in living cells, shedding light on many decades-old questions in molecular biology. From the contents: Structure of the Ribosome Ribosome Assembly tRNA and Synthetases mRNA Degradation Initiation and Elongation Termination and Ribosome Recycling Regulation of Ribosome Biosynthesis Inhibition of the Translational Apparatus by Antibiotics A premier resource for anyone with an interest in ribosomal protein synthesis, whether in the context of molecular biology, biotechnology, pharmacology or molecular medicine. |
 |
The Ribosome: Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVI by Cold Spring Harbor Laboratory (Author) This is the first book to contain the newly published findings on the structure of the ribosome and discuss their meaning for our understanding of how proteins are made and processed inside the cell. With over 60 contributions from the worldÂ’s most innovative ribosome biology laboratories, this is the latest volume in the annual series that for over 60 years has provided analysis and interpretation of the most interesting problems in biology. |
 |
Metabolic (Ribosome Edit) Jakt (Primary Contributor) |
 |
Ribosomes (Cellular Organelles) by Alexander S. Spirin (Author) Dr. Spirin is a world authority on ribosomes and has published two earlier books in this area in English. He is one of the best possible people who could write this book. This text is for advanced undergraduates and beginning graduate students and will cover the structure, function, and biosynthesis of ribosomes. Ribosomes are important in protein synthesis, which is currently a hot topic in many different areas of research. |
|
Pleasure or Pain Tracks are: 1. Do You Remember? 2. Pleasure Or Pain 3. Tango 4. Never Change 5. Average Guy 6. Chairman 7. Sweet Jane 8. Reckless Lover 9. Slide Aside 10. Slide Aside (Uncensored Mix) | |
|
The Ribosome: Structure, Function, & Evolution by Walter E. Hill (Author) "This book is recommended as a 'hitchhiker's guide to the ribosome' for everyone with an interest in translation, RNA-protein structures, and macromolecular structure-function relationships" Science. | |
|
Ribosome: An entry from Macmillan Reference USA's Macmillan Reference USA Science Library: Biology by Jon Lorsch (Author) This digital document is an article from Macmillan Reference USA Science Library: Biology, brought to you by Gale®, a part of Cengage Learning, a world leader in e-research and educational publishing for libraries, schools and businesses. The length of the article is 877 words. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. A comprehensive collection of articles on all aspects of biological science, including its history and issues. Includes articles on biology-related careers and important individuals, as well as topics from active transport to zoology research. | |
|
Ribosomes and RNA Metabolism by J. (ed) Zelinka (Author) | |
 |
Ribosomes Kenny Cambre (Primary Contributor) |
| © 2009 BrightSurf.com |