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Physical and biochemical studies of G-Protein coupled receptors

Our lab studies the structure and function of G-protein coupled receptors (GPCRs), a large family of membrane proteins crucial for transmitting signals into cells. We focus our studies on two GPCR systems, the visual photoreceptor rhodopsin, and the marijuana receptor (the human neuronal cannabinoid receptor).

One way we study these proteins is by combining physical and biochemical techniques. For example, we introduce spectroscopic labels at defined locations in the proteins, and monitor where and what kinds of conformational changes occur during their activation.

Ultimately we hope to identify common structural mechanisms involved in GPCR mediated signal transduction and regulation. We feel our intense focus on these receptors is justified; the majority of drugs in use work by affecting GPCR signaling. Thus, a better understanding of how GPCRs are activated should help in future drug development.
 

Recent Publications:

1. Fay JF, Dunham TD, Farrens DL. Cysteine Residues in the Human Cannabinoid Receptor: Only C257 and C264 Are Required for a Functional Receptor, and Steric Bulk at C386 Impairs Antagonist SR141716A Binding. Biochemistry. 2005 Jun 21;44(24):8757-69.

2. Sommer ME, Smith WC, Farrens DL. Dynamics of arrestin-rhodopsin interactions: arrestin and retinal release are directly linked events. J Biol Chem. 2005 Feb 25;280(8):6861-71. Epub 2004 Dec 9.

3. Janz JM, Farrens DL. Role of the retinal hydrogen bond network in rhodopsin Schiff base stability and hydrolysis. J Biol Chem. 2004 Dec 31;279(53):55886-94. Epub 2004 Oct 8.

4. Mansoor SE, Farrens DL. High-throughput protein structural analysis using site-directed fluorescence labeling and the bimane derivative (2-pyridyl)dithiobimane. Biochemistry. 2004 Jul 27;43(29):9426-38.