( s attached to the surface of the recept...)Nicotine rush hinges on sugar in neurons

“They serve as the link between the neurotransmitter binding site and the membrane region where the gate is located,” Chen said.

“The sugar is kind of like a hinge. It’s pulling the door open and closed.”

Cutting the sugar chains stopped the gate’s operation, according to Chen, who said, “The sugar is critical, in my opinion.”

The researchers also found a water molecule deep in the receptor’s core – significant because proteins normally are filled with hydrophobic (water repellent) matter that helps the structure hold its shape, Chen said.

The water molecule may enable the receptor to alter its shape in counterbalance to the bending hinge, said Chen, who explained, “Think of it as a lubricant.”

Previously studied “homologs” of nAChR – proteins that share its structure but not its signaling function – are entirely hydrophobic, Chen said, supporting the theory that the buried water molecule plays a functional role.

Chen called the group’s Nature Neuroscience study “one of the few times that you felt that you connected the dots.”

The study also represents a tour de force of protein crystallography. Homologs of nAChR had been studied at the atomic scale, but not the receptor itself.