Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Structure of 450 Million Year Old Protein Reveals Evolution’s Steps

Published: Wednesday, August 22, 2007
Last Updated: Wednesday, August 29, 2007
Bookmark and Share
Researchers have determined the atomic structure of an ancient protein, revealing in detail how genes evolved their functions.

A detailed map that pinpoints the location of every atom in a 450-million-year-old resurrected protein reveals the precise evolutionary steps needed to create the molecule’s modern version, according to researchers from the University of North Carolina at Chapel Hill and the University of Oregon.

Until now, scientists trying to unravel the evolution of the proteins and other molecules necessary for life have worked backwards, making educated guesses based on modern human body chemistry. By moving forward from an ancient protein, the team laid out the step-by-step progression required to reach its current form and function.

The study appeared online Aug. 16, 2007, in ScienceXpress.

“We were able to see exactly how mutations in the ancient structure led to the modern receptor,” said lead author Eric Ortlund, who carried out the research as a UNC-Chapel Hill postdoctoral fellow. Ortlund is now an assistant professor of biochemistry in the Emory University School of Medicine.

In the current study, Ortlund and Matt Redinbo, a professor of chemistry, biochemistry and biophysics at UNC-Chapel Hill, generated a three-dimensional picture of the ancient receptor with an imaging technique called X-ray crystallography. The nanoscale image revealed the receptor’s structure, down to the placement of every atom. With the structure in place, Ortlund and his colleagues retraced evolution’s path.

The researchers examined the precursor to a modern protein known as a glucocorticoid receptor. In humans, the receptor plays a crucial role, responding to the hormone cortisol and regulating the body’s stress response. The two – receptor and hormone – fit together as precisely as a lock and key. The precursor preferred a different hormone, so several mutations were necessary before the lock could fit the cortisol key.

The University of Oregon team, which included postdoctoral scientist Jamie Bridgham, resurrected the ancient protein via a large database of modern receptor genes. This earlier work, which compared the genetic similarities and differences among two of these modern genes, found the receptor descended from a single common genetic ancestor 450 million years ago. The researchers then recreated the ancient receptor in the laboratory.

Only seven mutations were needed to bridge the 450-million-year gulf, the researchers found. However, not every mutation changed the protein’s function. These permissive mutations appear to pave the way for future, more significant changes. “It’s like they prepared for opportunity to knock in the form of a new hormone,” Ortlund said.

The permissive mutations bolstered the receptor’s structure, like contractors reinforce a historic home’s foundation before making renovations. After these changes took place, a more extreme mutation repositioned an entire group of atoms, bringing them closer to fitting the cortisol hormone. Another created the tight new fit with cortisol.

“These permissive mutations are chance events. If they hadn’t happened first, then the path to the new function could have become an evolutionary road not taken,” said co-author Joe Thornton, a professor of evolutionary biology at the University of Oregon.

The researchers worked out which mutations came first by synthesizing different versions of the mutated protein in the laboratory. Had the radical mutations come first, the receptor protein would have lost its function entirely, they found.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More Than 5,000+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Mimicking Evolution to Create Novel Proteins
A study by researchers in the Kuhlman lab offers a new route to design the 'cellular machines' needed to understand and battle diseases.
Monday, May 16, 2016
Scientists Create Painless Patch of Insulin-Producing Beta Cells to Control Diabetes
Researchers at UNC and NC State have developed the new “smart cell patch” to treat millions of people with type-1 and advanced type-2 diabetes.
Saturday, March 19, 2016
Device Hits Pancreatic Tumors Hard With Toxic Four-Drug Cocktail, Sparing The Body
Researchers at UNC have revealed that an implantable device can deliver a particularly toxic cocktail of drugs directly to pancreatic tumors to stunt their growth and shrink them.
Saturday, February 27, 2016
Stem Cells Turned into Cancer Killers
Skin cells turned cancer-killing stem cells hunt down and destroy the deadly remnants inevitably left behind when a brain tumor is surgically removed.
Friday, February 26, 2016
Stem Cells Turned into Cancer Killers
Skin cells turned cancer-killing stem cells hunt down and destroy the deadly remnants inevitably left behind when a brain tumor is surgically removed.
Friday, February 26, 2016
Potential Brain Cancer Drug Target
UNC Lineberger researchers have reporedt that when they removed Dicer from preclinical models of medulloblastoma, a common type of brain cancer in children, they found high levels of DNA damage in the cancer cells, leading to the cells’ death.
Friday, January 08, 2016
New Path for ALS Drug Discovery
For the first time, scientists pin down the structure of toxic clumps of a protein associated with a large number of ALS cases, opening new avenues in the pursuit of drugs to stem the disease.
Thursday, January 07, 2016
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Monday, November 16, 2015
Autism Mutation Isolated – Could Be Treated with Specific Enzyme
The research shows the precise cellular mechanisms that could increase risk for the disorder and how an existing drug might help thousands of people with autism.
Monday, August 10, 2015
Researchers Find Two Biomarkers Linked to Severe Heart Disease
Study suggests that elevated oxidized LDL cholesterol and fructosamine – a measure of glycated proteins in blood sugar – are signposts for the development of severe coronary disease, especially in females.
Thursday, July 09, 2015
A Single-Cell Breakthrough
UNC School of Medicine scientist Scott Magness and collaborators use their newly developed technology to dissect properties of single stem cells. The advancement will allow researchers to study gastrointestinal disorders and cancers like never before.
Thursday, March 19, 2015
New Gene Therapy For Hemophilia Shows Potential As Safe Treatment
Research showed that bleeding events were drastically decreased in animals with hemophilia B. Using a viral vector to swap out faulty genes proved safe and could be used for the more common hemophilia A.
Tuesday, March 17, 2015
Genetically Speaking, Mammals Are More Like Their Fathers
A first of its kind study shows that who we inherit genetic variants from – our mother or father – is crucial for the development of diseases and for research studies aimed at finding causes and potential treatments.
Wednesday, March 04, 2015
Key Protein That Allows Plavix To Conquer Platelets Found
The findings could lead to more personalized approaches to controlling platelet activity during heart attacks and other vascular emergencies and diseases.
Wednesday, February 25, 2015
Researchers Silence Leading Cancer-Causing Gene
A novel siRNA-based molecule successfully targets KRAS, a well-studied but hard to halt protein important for cancer development and metastasis.
Monday, November 17, 2014
Scientific News
Point of Care Diagnostics - A Cautious Revolution
Advances in molecular biology, coupled with the miniaturization and improved sensitivity of assays and devices in general, have enabled a new wave of point-of-care (POC) or “bedside” diagnostics.
Mass Spec Technology Drives Innovation Across the Biopharma Workflow
With greater resolving power, analytical speed, and accuracy, new mass spectrometry technology and techniques are infiltrating the biopharmaceuticals workflow.
One Step Closer to Precision Medicine for Chronic Lung Disease Sufferers
A study led by University of North Carolina at Chapel Hill, and National Jewish Health, has provided evidence of links between SNPs and known COPD blood protein biomarkers.
Charles River Acquires Agilux
Enhances Charles River’s early-stage capabilities in bioanalytical services.
Scientists Find Lethal Vulnerability in Treatment-Resistant Lung Cancer
The study describes how the drug Selinexor killed lung cancer cells and shrank tumors in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene.
How Baby’s Genes Influence Birth Weight And Later Life Disease
The large-scale study could help to target new ways of preventing and treating these diseases.
Genes Underlying Dogs’ Social Ability Revealed
The social ability of dogs is affected by genes that also seem to influence human behaviour, according to a new study from Linköping University in Sweden.
Drug to Treat Alcohol Use Disorder Shows Promise Among Drinkers With High Stress
The findings suggest that potential future studies with drugs targeting vasopressin blockade should focus on populations of people with AUD who also report high levels of stress.
C Dots Show Powerful Tumor Killing Effect
Nanoparticles known as Cornell dots, or C dots, have shown great promise as a therapeutic tool in the detection and treatment of cancer.
Faecal Bacteria Linked to Body Fat
Researchers at King’s College London have found a new link between the diversity of bacteria in human poo – known as the human faecal microbiome - and levels of abdominal body fat.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!