Highlights of our Work
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Deciphering the nuts and bolts of the how the brain works is crucial for understanding human psychology and behaviors developing novel and more effective treatments for neurological diseases. The human brain's function relies on the transmission of electric signals from one neuron to another through the synapse, a delicate process mediated by diffusion of neurotransmitter molecules released from the presynaptic cell that bind their specific receptor on the postsynaptic cell. In a recent collaborative study, performed with the experimental lab of Eric Gouaux (Vollum Institute), one of the key receptors, known as the AMPA receptor, was characterized in its three major functional states: closed, desensitized and active (see Figure 1). The study has uncovered the long-sought structures for the active and desensitized states of this protein for the first time (using cryo-EM) after decades of research. These structures provide vital information as to how this ion channel receptor converts the chemical signal of the neurotransmitter to a temporally controlled excitation profile in the postsynaptic neuron. The method of MDFF developed by the Center was used for refinement of the structure, and NAMD simulations together with VMD visualization were used to characterize the open state of the channel.