Arthur Karlin

I am interested in the molecular mechanisms of membrane-protein function. Most of my effort has been on the nicotinic acetylcholine receptors, which were merely pharmacological concepts when I began. My laboratory identified the four different subunits of the muscle-type receptor (2 alpha, 1 beta, 1 gamma, and 1 delta) and showed that they assembled into a pentamer. It also showed that the two acetylcholine binding sites per receptor were associated with the two alpha subunits and later showed that binding-site residues in alpha were close to residues in the gamma and delta subunits, which also contributed to acetylcholine binding. We developed a combined mutational and chemical approach to identify all of the residues that line the ion-conducting channel of the receptor, to detect changes in the structure of the channel as it opened and closed, to map the electrostatic potential profile within the channel, and to locate the channel gate. This approach is being widely applied to other receptors, channels, and transport proteins.