Nature: Study Led by NIH Depicted the Specific Description of Brain Protein Structure
Researchers from National Institute of Neurological Disorders and Stroke (NINDS) have published the first highly detailed description of how a neuropeptide hormone, neurotensin, which been previously shown has correlation to Parkinson’s disease, schizophrenia, temperature regulation, pain, and cancer cell growth, interacts with its receptor. Neurotensin modulates nerve cell activity in the brain.
Their finding was published on Nature.
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. Their results suggest that neuropeptide hormones use a novel binding mechanism to activate a class of receptors called G-protein coupled receptors (GPCRs) by using X-ray crystallography. 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.
They found the binding of neurotensin initiates a series of reactions in nerve cells which may change the way scientists develop drugs targeting similar neuropeptide receptors.
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.
Published on Oct. 11, 2012, the results were the first X-ray crystallography studies showing how a neuropeptide agonist binds to neuropeptide GPCRs. While researcher told before totally understand, more work is needed to do to find out more information about signaling mechanism of this GPCR.
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.
Article Link: Nature: Study Led by NIH Depicted the Specific Description of Brain Protein Structure
Tags: Protein Structure, NIH, GPCR, Crystallography, Membrane Protein