Sugar is the key to the nicotine rush according to new research

The water molecule may enable the receptor to alter its shape in counterbalance to the bending hinge.

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. One problem, solved by Wang’s laboratory, was the challenge of isolating large quantities of the nAChR protein in a suitable form.

“Many prestigious institutions and laboratories in the world have experienced tremendous difficulties for over two decades in getting a protein sample amenable for high-resolution studies of the structure,” Wang said.

Cosma Dellisanti, research associate in molecular and computational biology at USC, was first author. The other co-authors were Yun Yao of the Keck School and James Stroud of UCLA.

Funding for the research came from the Muscular Dystrophy Association and the National Institutes of Health.