A Molecular Hinge Allows Transport Proteins to Move Neurotransmitters Across Brain Cell Membranes

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