Breaking News
October 20, 2018 - Pounds Regained After Weight-Loss Op Can Tell Your Doc a Lot
October 20, 2018 - Sending parents letters to fight childhood obesity doesn’t work
October 20, 2018 - Supervised aerobic exercise can support major depression treatment
October 20, 2018 - Mindfulness-based program effective for reducing stress in infertile women
October 20, 2018 - Molecule capable of halting and reverting neurodegeneration caused by Parkinson’s disease identified
October 20, 2018 - Midazolam-mediated alterations of PER2 expression may have functional consequences during myocardial ischemia
October 20, 2018 - Sweat bees are ideal for studying the genes underlying social behavior
October 20, 2018 - Weight loss success associated with brain areas involved in self-control
October 20, 2018 - KHN’s ‘What the Health?’ Republicans’ preexisting political problem
October 20, 2018 - Research provides a more complete picture of suffering caused by terrorist attacks
October 20, 2018 - Eradicating Helicobacter pylori infections may be a key treatment for Parkinson’s disease
October 20, 2018 - Breast Cancer as a Dynamic Disease
October 20, 2018 - University of Pittsburgh wins NSF grant for big data research to prevent complications from anesthesia
October 20, 2018 - Skin-to-skin contact may promote attachment between parents and preterm infants
October 20, 2018 - Recommendations Developed to Verify NGT Placement in Children
October 20, 2018 - Weight loss can be boosted fivefold thanks to novel mental imagery technique
October 20, 2018 - Children with autism are more likely to be overweight, obese
October 20, 2018 - Nurses making conscientious objections to ethically-relevant policies lack support
October 20, 2018 - Prion strain diversity may be greater than previously thought
October 20, 2018 - Antidepressant treatment may lead to improvements in sleep quality of patients with depression
October 20, 2018 - Study reports increased risk of death in children with inflammatory bowel disease
October 20, 2018 - Number of Autism Genes Now Tops 100
October 20, 2018 - Total diet replacement programmes are effective for treating obesity
October 20, 2018 - CLARIOstar used for fluorescence measurements on CSIRO’s purpose-built research vessel
October 20, 2018 - People with more copies of AMY1 gene digest starchy carbohydrates faster
October 20, 2018 - Case Comprehensive Cancer Center wins NIH grant to study health disparities
October 20, 2018 - Newly discovered compound shows potential for treating Parkinson’s disease
October 20, 2018 - High rate of non-adherence to hormonal therapy found among premenopausal early breast cancer patients
October 20, 2018 - Immunotherapy medicine found to be effective in treating uveitis
October 20, 2018 - The Pistoia Alliance Calls for Greater Collaboration to Realise Benefits of Innovation and Announces Winners of the 2018 President’s Startup Challenge
October 20, 2018 - Female internists consistently earn less than men
October 20, 2018 - Stanford team looks at dangers of teens’ vaping habits
October 20, 2018 - New approach to understanding cancers will accelerate development of better treatments
October 20, 2018 - LJI and UC San Diego awarded $ 4.5 million as part of NCI’s Cancer Moonshot initiative
October 20, 2018 - School-based HPV vaccination did not increase risky sexual behaviors among adolescent girls
October 20, 2018 - Eye discovery to pave way for more successful corneal transplants
October 20, 2018 - New analysis examines the importance of location in the opioid crisis
October 20, 2018 - Green filters increase reading speed for children with dyslexia
October 19, 2018 - Bariatric Sx Cuts Macrovascular Complications in Obesity, T2DM
October 19, 2018 - Better assessments for early age-related macular degeneration
October 19, 2018 - Visible and valued: Stanford Medicine’s first-ever LGBTQ+ Forum | News Center
October 19, 2018 - Understanding of metal-free enzymes used by bacteria could lead to new effective antibiotics
October 19, 2018 - Beckman Coulter Life Sciences announces new research-focused website
October 19, 2018 - Study finds link between refined soluble fibers, gut microbiota and liver cancer
October 19, 2018 - Social media reduces risk of depression among seniors with pain
October 19, 2018 - Newly developed synthetic DNA molecule may one day be used as ‘vaccine’ for prostate cancer
October 19, 2018 - Preoperative weight loss may not provide health benefits after surgery
October 19, 2018 - U.S. Birth Rates Continue to Drop as Age of New Moms Rises
October 19, 2018 - New technology can keep an eye on babies’ movements in the womb
October 19, 2018 - Juul e-cigarettes pose addiction risk for young users | News Center
October 19, 2018 - Gene sequencing reveals crucial molecular aspects of Trypanosoma brucei
October 19, 2018 - New DNA vaccine strategy protects mice against lethal challenge by multiple H3N2 viruses
October 19, 2018 - Study shows close link between cytokine interleukin-1ß and obesity-promoted colon cancer
October 19, 2018 - Muscle mass plays a critical role in health, shows research
October 19, 2018 - Study finds undiagnosed prediabetes in many infertile men
October 19, 2018 - The Current issue of “The view from here” is concerned with Nanotherapeutic strategies
October 19, 2018 - Delay in replacing the Pap smear with HPV screening is costing lives
October 19, 2018 - Physicians battle pediatric diseases of ear, nose, throat in Zimbabwe | News Center
October 19, 2018 - Researchers investigate why some cancers affect only young women
October 19, 2018 - Drugmakers funnel millions to lawmakers; a few dozen get $100,000-plus
October 19, 2018 - Unselfish people tend to have more children and receive higher salaries
October 19, 2018 - New findings reveal potential cellular players in tumor microenvironment
October 19, 2018 - Study reveals impact of Juul use on teenagers and young adults
October 19, 2018 - Green leafy vegetables could help reduce macular degeneration risk
October 19, 2018 - Some countries take more time for reimbursement decisions on new cancer drugs
October 19, 2018 - Human brain cell transplant offers insights into neurological conditions
October 19, 2018 - Parental education associated with increased family health care spending
October 19, 2018 - New statistical method estimates long- and short-term risk of recurrence of breast cancer in US women
October 19, 2018 - Father’s exposure to nicotine may cause cognitive deficits in descendants
October 19, 2018 - Could we prevent Alzheimer’s disease by treating herpes?
October 19, 2018 - Nurse-led care can be more successful in managing gout
October 19, 2018 - Trump administration, pharma exchange verbal volleys on drug-price transparency
October 19, 2018 - Duke researchers find way to detect blood doping in athletes
October 19, 2018 - Many primary care doctors are still prescribing sedative drugs for older adults
October 19, 2018 - Finger length can predict sexuality in women say researchers
October 19, 2018 - Study finds differences in side-effects experienced by male and female OG cancer patients
October 19, 2018 - Dysfunction of single gene leads to miscarriages
October 19, 2018 - Few Seniors Who Self-Harm Referred for Mental Health Care
October 19, 2018 - Don’t sweat the sweet stuff
October 19, 2018 - URMC researchers discover new approach to deliver therapeutics to the brain
Scientists decipher workings of little-understood bacterial riboswitch

Scientists decipher workings of little-understood bacterial riboswitch

image_pdfDownload PDFimage_print

In a discovery that points to potential new antibiotic medicines, scientists from Rice University and the University of Michigan have deciphered the workings of a common but little-understood bacterial switch that cuts off protein production before it begins.

Many gram-positive bacteria use T-box riboswitches to regulate production of proteins that utilize amino acids, the basic building blocks of all proteins. A study in Nature Communications describes how one of these switches, a glycine regulator in Bacillus subtilis, flips and locks into the “on” position via a snap-lock mechanism. Engaging the lock increases production of proteins that utilize glycine, the simplest amino acid. Researchers also detailed the switch’s “off” position: A single glycine at the tip of the locking arm blocks protein production.

“T-box riboswitches are intriguing because they are regulated — turned on or off — by molecules central to protein production,” said study co-author Edward Nikonowicz, professor of biosciences at Rice. “While they were discovered a quarter century ago, it’s not been entirely clear how they operate. By highlighting their structural and kinetic details, we hope to spur interest in these switches as potential targets for new antibiotics.”

New antibiotics could help avert a looming health crisis, Nikonowicz said. The Centers for Disease Control and Prevention expects antibiotic-resistant bacteria to kill at least 23,000 people in the U.S. this year, and if current trends go unchecked, the World Health Organization estimates that by 2050, drug-resistant pathogens will kill 10 million people per year worldwide.

T-box riboswitches like the one highlighted in the new study are vital to many gram-positive bacteria, a broad class that includes pathogens that cause tuberculosis, gangrene, botulism, anthrax, inflammation of the inner heart lining and other diseases.

T-box riboswitches are located on strands of messenger RNA (mRNA), blueprints for proteins that are copied directly from a cell’s DNA. In complex organisms such as animals and plants, the writing, or “transcription,” of mRNA takes place in a vault-like DNA storage facility called the nucleus. Only after mRNA leaves the vault can its message be used, or “translated,” into a new protein. Because bacteria have no nucleus, “transcription” of mRNA and “translation,” decoding of mRNA by ribosomes to make new proteins, happen in close proximity.

“Riboswitches are common in many bacteria, but not in humans, making them such attractive targets for new drugs,” said study co-author Nils Walter, the Francis S. Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry at the University of Michigan. “T-box riboswitches regulate transcription, the writing of the messenger RNA itself, but use a locking arm borrowed from the translation machinery, making it a unique jack-of-all-trades.”

The mRNA blueprints are used to build proteins, the workhorses of biology. Cells employ millions of proteins at a given time, but each of these is made from the same 20 building blocks, the amino acids that T-box riboswitches help regulate in gram-positive bacteria. To make a protein, cells string amino acids end to end, like beads on a necklace, based on the order specified in mRNA instructions.

The locking arm trigger in the glycine T-box riboswitch is part of another molecule called transfer RNA (tRNA). There are many types of tRNA in cells, but each acts like a kind of car, shuttling payloads to the ribosome, where proteins are strung together. Each type of tRNA can only carry one type of amino acid.

In the new study, Walter and Nikonowicz designed an experiment in which glycine-specific tRNA molecules, some loaded with glycine and others unloaded, would pass by and randomly attach to a T-box riboswitch.

“Ed’s team was able to attach a fluorescent marker to the tRNA in a such a way that it wouldn’t interfere with their binding,” Walter said. “My lab employed a technique called ‘single molecule fluorescence microscopy’ to probe the dynamic associations of single T-box riboswitches with the tRNA, either when the glycine cargo was attached or not.”

Each time a tRNA with a fluorescent tag attached took up a position on the T-box riboswitch, a bright signal appeared in the microscope. By measuring exactly how long the signal lasted, and thus how long the molecules stayed in position, the team was able to reconstruct the binding speed and ultimately the locking mechanism for the switch.

Nikonowicz said he and Walter began the glycine T-box riboswitch project about 2 1/2 years ago.

“Glycine was the simplest case, in part because there’s an additional domain in the T-box sensing other amino acids,” he said. “There are questions about what this domain does and how it operates. Given what we’ve already learned about the glycine T-box riboswitch, I’d like to extend this work to see what we can learn from other types of T-boxes.”

Walter added the findings could also pay off in the emerging field of RNA nanotechnology, in which scientists are attempting to use RNA templates for precision engineering of complex structures.

“In the active, locked position, the T-box-tRNA complex has a very stable three-dimensional shape,” he said. “It’s possible these could be exploited for ultra-stable ring-like complexes in novel biomimetic architectures.”

Source:

Study finds snap-lock mechanism in bacterial riboswitch

Tagged with:

About author

Related Articles