JUL 02, 2020 6:35 PM PDT

The Intricate Movements of a Critical Receptor are Revealed

WRITTEN BY: Carmen Leitch

Scientists have now learned more about a critical protein in the brain called the NMDA receptor, tracking every atom as brain signals are transmitted through it. The receptor can be found at synapses, where neurons meet and release neurotransmitters. The NMDA or N-Methyl-D-Aspartate receptor, for example, is responsive to the neurotransmitter glutamate. Using cryo-electron microscopy, scientists have unlocked the details of how it opens and shuts. The findings have been reported in Cell.

The NMDA receptor sits in the membrane of neuronal cells; its channel spans the membrane and it has a binding section that protrudes from the cell. When glycine and glutamic acid bind to the receptor, it rocks, and small filaments pull on a gate that opens the channel. When a receptor antagonist binds to the receptor, it gets rocked in another way, the filaments come loose, and the gate closes. These mechanistic insights may help us learn more about diseases that involve the brain and the NMDA receptor, including epilepsy, depression, stroke, or schizophrenia.

"This is all happening because the subunit arrangement changes quite dramatically upon binding to the inhibitor. It all comes down to the stretching and non-stretching of the loop between the ligand-binding domain and the ion channel. They're really a series of conformations or events that are happening outside [the cell], and it eventually gets translated to the ion channel activity," said the study leader, Cold Spring Harbor Laboratory (CSHL) Professor Hiro Furukawa.

When glycine and glutamate bind to the NMDA receptor at its ligand-binding domain (LBD), the LBD rolls around, generating a loop that grabs a transmembrane domain. This domain forms the channel through the receptor, so as the LBD rolls, the transmembrane domain, which has been grabbed, is also stretched. This stretching pulls apart the amino acids that form the pore.

This work may help researchers create medications that can control the activity of the NMDA receptor with greater precision. The receptor is thought to play a role in a wide variety of disorders. The study may also help scientists apply the work to other receptors to unlock their mysteries.

Sources: Phys.org via CSHL, Cell

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 13, 2020
Cell & Molecular Biology
RNA Found on the Surface of Human Cells
SEP 13, 2020
RNA Found on the Surface of Human Cells
The surface of a cell carries many features to help it carry out its functions, communicate with other cells, gather inf ...
SEP 14, 2020
Microbiology
The Immune System Can Kill HIV with a Helper Molecule
SEP 14, 2020
The Immune System Can Kill HIV with a Helper Molecule
HIV attacks the human immune system's CD4 cells, a major player in the body's defense against pathogens.
SEP 19, 2020
Cell & Molecular Biology
Reward and Punishment Take Similar Paths in the Mouse Brain
SEP 19, 2020
Reward and Punishment Take Similar Paths in the Mouse Brain
Scientists have determined that mice have brain cells that can help them learn to avoid bad experiences.
OCT 12, 2020
Cell & Molecular Biology
The Human Arm Appears to be Evolving Slightly
OCT 12, 2020
The Human Arm Appears to be Evolving Slightly
There are no humans that can perform feats of super-strength or control objects with their mind, but people are apparent ...
NOV 11, 2020
Health & Medicine
A smart path for novel biologics
NOV 11, 2020
A smart path for novel biologics
Introduction  Cell culture is at the heart of the production process for many biopharmaceuticals, but finding the o ...
NOV 11, 2020
Cell & Molecular Biology
Visualizing a Tumor Suppressor in Action
NOV 11, 2020
Visualizing a Tumor Suppressor in Action
Many types of cells in our bodies are short-lived and need to be replenished. Cell division has to be carefully controll ...
Loading Comments...