ARTHUR KARLIN

The research of the laboratory is aimed at the function of receptors in terms of molecular structures. We try to understand how receptors recognize specific ligands, how the binding of these ligands is converted into the opening of ion-conducting channels (or into an interaction with GTP-binding proteins), how the selectivity of the channels is determined, and how ions are conducted through the channels. The main approaches are to identify the residues that line the binding sites and conduction pathways, to determine the three-dimensional structures, to locate the critical residues in these three-dimensional structures, and to detect changes in the structures corresponding to changes in functional states. To reach these goals, we use the methods of protein chemistry, molecular biology, and electrophysiology.

Selected Publications

Karlin, A., and Akabas, M.H. 1995. Toward a structural basis for the function of the nicotinic acetylcholine receptors and their cousins. Neuron 15:1231-1244.

Sun, Z.-p., Akabas, M.H., Goulding, E.H., Karlin, A., and Siegelbaum, S.A. 1996. Exposure of residues in the cyclic nucleotide-gated channel pore: P-region structure and function in gating. Neuron 16:141-149.

Martin, M., Czajkowski, C., and Karlin, A. 1996. The contributions of aspartyl residues in the acetylcholine receptor gamma and delta subunits to the binding of agonists and competitive antagonists. J. Biol. Chem. 271:13497-13503.

Martin, M.D., and Karlin, A. 1997. The functional effects on the acetylcholine receptor of multiple mutations of gamma Asp174 and delta Asp180. Biochemistry 36:10742-10750.

Wilson, G.G. and Karlin, A. 1998. The location of the gate in the acetylcholine receptor channel. Neuron 20:1269-1281.

Zhang, H., and Karlin, A. 1997. Identification of acetylcholine receptor channel-lining residues in the M1 segment of the ß subunit. Biochemistry 36:15856-15864.

Karlin, A., and Akabas, M.H. 1998. Substituted-cysteine accessibility method. In "Methods in Enzymology: Ion Channels", editor P. Michael Conn, Academic Press, San Diego, Vol. 293, pp. 123-145.

Pascual, J.M., and Karlin, A. 1998. State-dependent accessibility and electrostatic potential in the channel of the acetylcholine receptor: Inferences from rates of reaction of thiosulfonates with substituted cysteines in the M2 segment of the alpha subunit. J. Gen. Physiol. 111:717-739.

Zhang, H., and Karlin, A. 1998. Contribution of the ß subunit M2 segment to the ion-conducting pathway of the acetylcholine receptor. Biochemistry 37: 7952-7964.

Pascual, J.M., and Karlin, A. 1998. Delimiting the binding site for quaternary ammonium lidocaine derivatives in the acetylcholine receptor channel. J. Gen. Physiol. 112: 611-621.