PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Scientists devise innovative method to profile and predict the behavior of proteins

2013-08-08
(Press-News.org) SAN FRANCISCO, CA and COLLEGE STATION, TX—August 8, 2013—An enzyme is a tiny, well-oiled machine. A class of proteins that are made up of multiple, interlocking molecular components, enzymes perform a variety of tasks inside each cell. However, precisely how these components work together to complete these tasks has long eluded scientists. But now, a team of researchers has found a way to map an enzyme's underlying molecular machinery, revealing patterns that could allow them to predict how an enzyme behaves—and what happens when this process disrupted.

In the latest issue of the journal Cell, a team of scientists led by Gladstone Institutes and University of California, San Francisco (UCSF) Investigator Nevan Krogan, PhD, Texas A&M University's Craig Kaplan, PhD, and UCSF Professor Christine Guthrie, PhD, describe a new technique—called the point mutant E-MAP (pE-MAP) approach—that gives researchers the ability to pinpoint and map thousands of interactions between each of an enzyme's many moving parts.

The researchers focused on a well-known enzyme—called RNA polymerase II (RNAPII)—and used the single-cellular yeast species S. cerevisiae as a model. Researchers had previously mapped the physical structure of RNAPII, but not how various parts of the enzyme work with other proteins within the cell to perform vital functions.

"Scientists know RNAPII's physical structure, but this large enzyme has many distinct regions that each perform distinct functions" said Dr. Kaplan, who is also a scientist at Texas A&M AgriLife. "We wanted to connect the dots between these regions and their function."

In laboratory experiments, the team took a genetic approach—generating 53 variations of RNAPII, so-called RNAPII "mutants," that each changed a specific part of RNAPII. They wanted to test each mutant against a particular function. In this way, they could link a specific region in the enzyme to a specific function.

But to do so, they had to compare each of the mutants against thousands of functions that RNAPII might be involved in within the cell—an immense task that couldn't be accomplished by traditional methods. So the team developed the pE-MAP approach.

"Instead of crossing a single point mutant with one or two different mutants, pE-MAP lets us cross each one with more than 1,000," said Dr. Krogan, who also directs the California Institute for Quantitative Biosciences, or QB3, at UCSF. "This gives us 1,000 data points for each mutant, which we then use to build our high-resolution profiles."

"Until now, the only way to get similar information was to deactivate, or "knock out" specific genes within an enzyme and observe the impact," explained Hannes Braberg, a graduate student in Dr. Krogan's lab and the paper's lead author. "But RNAPII is so critical that deactivating even one gene often kills the cell. So instead of knocking out the genes, we mutated them."

The team then correlated the newly generated profiles to how well each variation of RNAPII could transcribe DNA into RNA—the enzyme's most important function. The research team found that some of the RNAPII mutants transcribed more slowly than the others, while others were much faster. Further analysis revealed that the slow transcribers showed key similarities with each other, as did the fast transcribers. A pattern began to emerge that allowed them to predict the transcription speed—fast or slow—for each mutant.

And then the team discovered yet another phenomena related to transcription, involving a process called splicing, whereby specific stretches of non-coding RNA are cut out, and what remains is stitched back together. Previously, scientists had hypothesized that the transcription speed was related to splicing—in that fast transcribers would be less accurate splicers, and vice versa. But no one had been able to see it in action. So Dr. Guthrie, whose lab researches splicing, used the profiles generated from the pE-MAP approach to observe in real time how different transcription speeds affected splicing precision.

"When you slow down transcription, splicing gets more efficient," said Dr. Guthrie. "We saw the opposite effect in our fast transcribers—which had long been predicted but had never before been observed. This was another testament to the power of the pE-MAP approach."

The approach used here could be applied to studies of other enzymes, explained the authors. And what the researchers learn could then be used to develop an understanding of how mutations in enzymes like RNAPII lead to specific disease states—and may ultimately inform our ability to correct them.



INFORMATION:



This research received support from QB3, the National Institutes of Health, the National Science Foundation, the Searles Scholars Program and the W.M. Keck Foundation.

About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.

About Texas A&M AgriLife

A part of The Texas A&M University System, Texas A&M AgriLife programs have revolutionized cotton harvesting, improved irrigation systems, increased rice and other grain yields, and harnessed biomass for fuel. AgriLife teaching and training have markedly enhanced the body of knowledge available to agriculture and the life sciences and have greatly increased leadership and education in these fields. Texas A&M AgriLife touches lives in Texas and across the United States and reaches out to the global community.



ELSE PRESS RELEASES FROM THIS DATE:

Kids born small should get moving

2013-08-08
HOUSTON – (Aug. 8, 2013) – Female mice who were growth restricted in the womb were born at a lower birth weight, but were less active and prone to obesity as adults, said researchers from Baylor College of Medicine and the USDA/ARS Children's Nutrition Research Center (CNRC) at BCM and Texas Children's Hospital in a report that appears online in the International Journal of Obesity. "Given that human studies also show female-specific obesity following early growth restriction," said Dr. Robert Waterland, associate professor of pediatrics – nutrition at BCM, and a member ...

Scientific breakthrough reveals how vitamin B12 is made

2013-08-08
Vitamin B12 is pieced together as an elaborate molecular jigsaw involving around 30 individual components. It is unique amongst the vitamins in that it is only made by certain bacteria. In the early 1990's it was realised that there were two pathways to allow its construction – one that requires oxygen and one that occurs in the absence of oxygen. It is this so-called anaerobic pathway, which is the more common pathway, that proved so elusive as the components of the pathway are very unstable and rapidly degrade. However, as explained in a paper published by PNAS (Proceedings ...

New forensic technique for analyzing lipstick traces

2013-08-08
Using a technique called Raman spectroscopy, which detects laser light, forensic investigators will be able to analyse lipstick marks left at a crime scene, such as on glasses, a tissue, or cigarette butts, without compromising the continuity of evidence as the sample will remain isolated. Analysis of lipstick traces from crime scenes can be used to establish physical contact between two individuals, such as a victim and a suspect, or to place an individual at a crime scene. The new technique is particularly significant for forensic science as current analysis of lipstick ...

Cesareans weaken gut microbiota and increase risk of allergies

2013-08-08
Children who came into the world by Caesarean section are more often affected by allergies than those born in the natural way. The reason for this may be that they have a less diverse gut microbiota, according to a study by universities in Sweden and Scotland. The researchers have followed gut macrobiota development in 24 children up to the age of two in the Swedish provinces of Östergötland and Småland, nine delivered through Caesarean and 15 delivered naturally, through vaginal birth. They used a type of molecular biology analysis, which gives a broad overview of the ...

Chemists' work will aid drug design to target cancer and inflammatory disease

2013-08-08
BLOOMINGTON, Ind. -- Chemists at Indiana University Bloomington have produced detailed descriptions of the structure and molecular properties of human folate receptor proteins, a key development for designing new drugs that can target cancer and inflammatory diseases without serious side effects. The researchers, from the lab of Charles Dann III, assistant professor of chemistry in the College of Arts and Sciences, published their findings in the Proceedings of the National Academy of Sciences. Dann said the results should help chemists create more effective antifolate ...

Carnegie Mellon research shows cellphone use may not cause more car crashes

2013-08-08
PITTSBURGH—For almost 20 years, it has been a wide-held belief that talking on a cellphone while driving is dangerous and leads to more accidents. However, new research from Carnegie Mellon University and the London School of Economics and Political Science suggests that talking on a cellphone while driving does not increase crash risk. Published in the American Economic Journal: Economic Policy, the study uses data from a major cellphone provider and accident reports to contradict previous findings that connected cellphone use to increased crash risk. Such findings ...

Terahertz technology fights fashion fraud

2013-08-08
The UK fashion industry is famous all over the world and worth around £37 billion to the economy. However, it is estimated that counterfeit clothing and footwear costs designer brands and retailers around £3.5 billion each year. Recently, new powers were given to customs officers to seize and destroy fake goods but in order to act on these powers they need to be able to tell whether or not a particular item of clothing is the genuine article. Scientists from the National Physical Laboratory (NPL) have published research in Applied Optics that demonstrates how a technique ...

TUM researchers investigate 59 tumor cell lines

2013-08-08
In what is the biggest study of its kind to date, researchers from Technische Universität München (TUM) have identified over 10,000 different proteins in cancer cells. "Nearly all anti-tumor drugs are targeted against cellular proteins," says Prof. Bernhard Küster, Head of the TUM Chair of Proteomics and Bioanalytics. "Identifying the proteome the protein portfolio of tumor cells increases our chances of finding new targets for drugs." The scientists investigated 59 tumor cell lines from the US National Cancer Institute. The "NCI-60" cell lines represent the most common ...

Fast detector for a wide wavelength range

2013-08-08
Free-electron lasers are extremely versatile research tools because their intense, super short light flashes permit a closer look at new materials and even biological molecules; thus, allowing effects to be observed that had not been known previously. For pulsed lasers in the far infrared range, the so-called terahertz range, scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) have developed a robust and fast detector which can measure the arrival of a terahertz pulse with great accuracy. The results were published in the scientific journal Applied Physics Letters ...

Study shows who survives Burkitt lymphoma

2013-08-08
A new study in the journal Cancer that tracked survival of more than 2,200 adults over the last decade with a highly aggressive form of lymphoma finds that with notable exceptions, medicine has made substantial progress in treating them successfully. To help doctors and researchers better understand who responds well to treatment and who doesn't, the study authors used their findings to create a stratified risk score of patient prognosis. Burkitt Lymphoma is not a common lymphoma but it is especially aggressive. The apparent progress doctors have made over the last two ...

LAST 30 PRESS RELEASES:

Echidnapus identified from an ‘Age of Monotremes’

Semaglutide may protect kidney function in individuals with overweight or obesity and cardiovascular disease

New technique detects novel biomarkers for kidney diseases with nephrotic syndrome

Political elites take advantage of anti-partisan protests to disrupt politics

Tiny target discovered on RNA to short-circuit inflammation, UC Santa Cruz researchers find

Charge your laptop in a minute? Supercapacitors can help; new research offers clues

Scientists discover CO2 and CO ices in outskirts of solar system

Theory and experiment combine to shine a new light on proton spin

PKMYT1, a potential ‘Achilles heel’ of treatment resistant ER+ breast cancers with the poorest prognosis

PH-binding motifs as a platform for drug design: Lessons from protease-activated receptors (PARs)

Virginia Tech researcher creates new tool to move tiny bioparticles

On repeat: Biologists observe recurring evolutionary changes, over time, in stick insects

Understanding a broken heart

Genetic cause of rare childhood immune disorders discovered

With wobbling stars, astronomers gauge mass of 126 exoplanets and find 15 new ones

High H5N1 influenza levels found in mice given raw milk from infected dairy cows

Study finds discreet shipping used to sell e-cigarettes to minors

African scientists call for equitable research partnerships to advance microbiome research

How COVID-19 'breakthrough' infections alter your immune cells

Virginia Tech entomologist sheds light on 250-year-old mystery of the German cockroach

Advancing skin science: explore Skin Ageing & Challenges 2024 Strategic Topics in Malta this November

Controlling water, transforming greenhouse gases

MSK Research Highlights, May 24, 2024

ASCO: Large precision oncology study identifies differences in prostate cancer genomics among a racially and ethnically diverse cohort of U.S. veterans

ASCO: Combination therapy significantly improves outcomes for patients with metastatic colorectal cancer

Euclid space mission releases first scientific results and new images of the cosmos

Sociodemographic heterogeneity in the associations of social isolation with mortality

COVID-19 admission rates and changes in care quality in us hospitals

Preterm and early-term delivery after heat waves in 50 US metropolitan areas

Research spotlight: Virtual scribes reduced physicians’ time spent on electronic health records

[Press-News.org] Scientists devise innovative method to profile and predict the behavior of proteins