Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

NIH Researchers Provide Detailed View of Brain Protein Structure

Published: Monday, October 22, 2012
Last Updated: Monday, October 22, 2012
Bookmark and Share
Results may help improve drugs for neurological disorders.

Researchers have published the first highly detailed description of how neurotensin, a neuropeptide hormone which modulates nerve cell activity in the brain, interacts with its receptor. Their results suggest that neuropeptide hormones use a novel binding mechanism to activate a class of receptors called G-protein coupled receptors (GPCRs).

"The knowledge of how the peptide binds to its receptor should help scientists design better drugs," said Dr. Reinhard Grisshammer, a scientist at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and an author of the study published in Nature.

Binding of neurotensin initiates a series of reactions in nerve cells. Previous studies have shown that neurotensin may be involved in Parkinson’s disease, schizophrenia, temperature regulation, pain, and cancer cell growth.

Dr. Grisshammer and his colleagues used X-ray crystallography to show what the receptor looks like in atomic detail when it is bound to neurotensin. Their results provide the most direct and detailed views describing this interaction which may change the way scientists develop drugs targeting similar neuropeptide receptors.

X-ray crystallography is a technique in which scientists shoot X-rays at crystallized molecules to determine a molecule’s shape and structure. The X-rays change directions, or diffract, as they pass through the crystals before hitting a detector where they form a pattern that is used to calculate the atomic structure of the molecule. These structures guide the way scientists think about how proteins work.

Neurotensin receptors and other GPCRs belong to a large class of membrane proteins which are activated by a variety of molecules, called ligands. Previous X-ray crystallography studies showed that smaller ligands, such as adrenaline and retinal, bind in the middle of their respective GPCRs and well below the receptor’s surface. In contrast, Dr. Grisshammer’s group found that neurotensin binds to the outer part of its receptor, just at the receptor surface. These results suggest that neuropeptides activate GPCRs in a different way compared to the smaller ligands.

Forming well-diffracting neuropeptide-bound GPCR crystals is very difficult. Dr. Grisshammer and his colleagues spent many years obtaining the results on the neurotensin receptor. During that time Dr. Grisshammer started collaborating with a group led by Dr. Christopher Tate, Ph.D. at the MRC Laboratory of Molecular Biology, Cambridge, England. Dr. Tate’s lab used recombinant gene technology to create a stable version of the neurotensin receptor which tightly binds neurotensin. Meanwhile Dr. Grisshammer’s lab employed the latest methods to crystallize the receptor bound to a short version of neurotensin.

The results published today are the first X-ray crystallography studies showing how a neuropeptide agonist binds to neuropeptide GPCRs. Nonetheless, more work is needed to fully understand the detailed signaling mechanism of this GPCR, said Dr. Grisshammer.

This study was supported by NINDS; the National Institute of Diabetes and Digestive and Kidney Diseases; Protein Production Facility of the New York Consortium on Membrane Protein Structure, New York City; and the MRC Laboratory of Molecular Biology.

Further Information
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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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 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

Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
NIH Framework Points The Way Forward For Developing The President’s Precision Medicine Initiative
The NIH Advisory Committee to the Director has presented to NIH Director Francis S. Collins, M.D., Ph.D., a detailed design framework for building a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine.
Monday, September 21, 2015
Beth Israel Cardiology Team Awarded $3 Million by NIH
Work will help predict outcomes in patients with heart disease.
Friday, September 18, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Scientists Uncover Nuclear Process in the Brain that May Affect Disease
NIH-funded study highlights the possible role of glial brain cells in neurological disorders.
Tuesday, August 18, 2015
PINK1 Protein Crucial for Removing Broken-Down Energy Reactors
NIH study suggests potential new pathway to target for treating ALS and other diseases.
Thursday, August 13, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Researchers Identify Protein in Mice that Helps Prepare for Healthy Egg-sperm Union
Protein RGS2 plays a critical role in preserving the fertilizability of the ovulated egg.
Wednesday, August 05, 2015
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Tuesday, August 04, 2015
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
Monday, August 03, 2015
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Monday, July 27, 2015
NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
Scientific News
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Gut Microbes Signal to the Brain When They're Full
Don't have room for dessert? The bacteria in your gut may be telling you something.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Novel Proteins Linked to Huntington's Disease
University of Florida Health researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos