Corporate Banner
Satellite Banner
Biomolecular Screening
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

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 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
NIH Awards Nearly $35 Million to Research Natural Products
Innovative Research Centers Program investigates botanical dietary supplements and other natural products.
Thursday, September 10, 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
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
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Possible Treatment for Lethal Pediatric Brain Cancer
NIH-funded preclinical study suggests epigenetic drugs may be used to treat leading cause of pediatric brain cancer death.
Tuesday, May 05, 2015
HIV can Spread Early, Evolve in Patients' Brains
Findings add urgency to screening, treatment - NIH-funded study.
Saturday, March 28, 2015
Test Reliably Detects Inherited Immune Deficiency in Newborns
NIH-supported study suggests that early diagnosis of severe combined immunodeficiency leads to high survival rates.
Thursday, August 21, 2014
NIH Names New Clinical Sites in Undiagnosed Diseases Network
Four-year, $43 million initiative engages broad expertise in study of mystery conditions.
Wednesday, July 02, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
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.
Potential Persistent Tuberculosis Treatment
Researchers have discovered several first-in-class compounds that target hidden TB infections by attacking a critical process the bacteria use to survive in the hostile environment of the lungs.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
The Do’s and Don’ts of SPR Experiments
Surface Plasmon Resonance (SPR) is a technique that is becoming more widely used, particularly by anyone who wants to obtain accurate on (association) and off (dissociation) rates for biomolecular binding.
Long-Sought Protein Sensor for the ‘Sixth Sense’ Discovered
In a study led by scientists from The Scripps Research Institute (TSRI)the sensor protein for propioception has been identified.
New Anti-Malarial Drug Screening Model
University of South Florida researchers demonstrate novel chemogenomic profiling to identify drug targets for the most lethal strain of malaria.
Shedding Light on “Dark” Cellular Receptors
UNC and UCSF labs create a new research tool to find homes for two orphan cell-surface receptors, a crucial step toward finding better therapeutics and causes of drug side effects.
New, Better Test for Prostate Cancer
A study from Karolinska Institutet shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA.
Giant Molecules Inhibit Ebola Infection
European researchers have designed a "giant" molecule formed by thirteen fullerenes covered by carbohydrates which, by blocking this receptor, are able to inhibit the cell infection by an artificial ebola virus model.

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