A Molecular Hinge Allows Transport Proteins to Move Neurotransmitters Across Brain Cell Membranes
By LabMedica International staff writers Posted on 13 May 2013 |
Image: Senior author Dr. Shimon Schuldiner (Photo courtesy of the Hebrew University of Jerusalem).
An international team of molecular biologists has developed a model that shows how components of a protein transport complex act as a molecular hinge to move neurotransmitters across brain cell membranes.
Investigators at the Hebrew University of Jerusalem (Israel) and the Max Planck Institute of Biophysics (Frankfurt am Main, Germany) focused on vesicular monoamine transporter 2 (VMAT2), a member of the largest superfamily of transporters, which is known to convey a variety of neurotransmitters such as adrenaline, dopamine, and serotonin as well as MPP, a neurotoxin linked to Parkinson’s disease.
In the April 9, 2013, issue of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) they described the importance of two anchor points positioned between two six-transmembrane-helix bundles. These two domains provide hinge points about which the two halves of the protein flex and straighten to open and close the translocation pathway, a process that enables alternating exposure of the substrate-binding site. Polar residues that create a hydrogen bond cluster form one of the anchor points of VMAT2, while the other results from hydrophobic interactions.
The investigators, led by Dr. Shimon Schuldiner, professor of biochemistry at the Hebrew University of Jerusalem, said that, "They hope that this knowledge may, in the future, help in designing drugs for treating pathologies involving transporters similar to VMAT, including infectious and neurological diseases."
Related Links:
Hebrew University of Jerusalem
Max Planck Institute of Biophysics
Investigators at the Hebrew University of Jerusalem (Israel) and the Max Planck Institute of Biophysics (Frankfurt am Main, Germany) focused on vesicular monoamine transporter 2 (VMAT2), a member of the largest superfamily of transporters, which is known to convey a variety of neurotransmitters such as adrenaline, dopamine, and serotonin as well as MPP, a neurotoxin linked to Parkinson’s disease.
In the April 9, 2013, issue of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) they described the importance of two anchor points positioned between two six-transmembrane-helix bundles. These two domains provide hinge points about which the two halves of the protein flex and straighten to open and close the translocation pathway, a process that enables alternating exposure of the substrate-binding site. Polar residues that create a hydrogen bond cluster form one of the anchor points of VMAT2, while the other results from hydrophobic interactions.
The investigators, led by Dr. Shimon Schuldiner, professor of biochemistry at the Hebrew University of Jerusalem, said that, "They hope that this knowledge may, in the future, help in designing drugs for treating pathologies involving transporters similar to VMAT, including infectious and neurological diseases."
Related Links:
Hebrew University of Jerusalem
Max Planck Institute of Biophysics
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples