Klaus Gawrisch, Ph.D.
Laboratory of Membrane Biochemistry and Biophysics
5625 Fishers Lane
Bethesda, MD 20892
Dr. Gawrisch's laboratory conducts structural and functional studies on reconstituted G protein- coupled membrane receptors (GPCR) including cannabinoid receptors and the visual receptor rhodopsin. The GPCR are recombinantly expressed or purified from a natural source, reconstituted into a fluid lipid matrix with a biologically relevant composition of lipids, and receptor activation and G protein signaling investigated at functional conditions. The laboratory pays particular attention to the mechanisms by which lipids influence receptor function, especially lipids with polyunsaturated hydrocarbon chains like docosahexaenoic acid, an omega-3 fatty acid found at high concentrations in brain. The primary experimental tool of the laboratory is solid-state nuclear magnetic resonance (NMR) which is applied on the GPCR and the surrounding lipid matrix. The goal of the investigations is a better understanding of the molecular mechanisms of receptor signaling including ligand binding, structural changes of the receptor induced by ligands, as well as G protein activation.
The cannabinoid receptors belong to the class of rhodopsin-like receptors, are one of the most ubiquitous GPCR, and have attracted much attention because of their role in health and disease. They are also remarkable because their endogenous ligands, 2-arachidonylglycerol (2-AG) and N-arachidonylethanolamine (anandamide), are synthesized from lipid-bound, polyunsaturated arachidonic acid, an omega-6 fatty acid. Rhodopsin, the mammalian dim-light photoreceptor is one of the best characterized GPCR and ideally suited to study the importance of polyunsaturated lipids for GPCR function. Membrane composition strongly modulates formation of photointermediates of rhodopsin. The similarities in structure and function of class A, rhodopsin-like GPCR suggest that results on lipid-rhodopsin interaction can be generalized to function of other GPCR.
Dr. Gawrisch was born in Freyburg, Germany in 1950. He received training in biophysics in the laboratory of Lev A. Blumenfeld and a Master's Degree in Physics from Moscow State University, Russia, in 1975. In Leipzig, at the laboratories of Gotthard Klose and Klaus Arnold he was trained in membrane biophysics and Nuclear Magnetic Resonance (NMR) and received a Ph.D. in Physics in 1979 and the Habilitation in Physics in 1986 both from the University of Leipzig, Germany. Until 1989 he served as Docent in Physics and Biophysics at the University of Leipzig. In 1989 he joined the laboratory of Adrian Parsegian at the Division of Computer Research and Technology and later the NMR laboratory of James Ferretti at the National Heart Lung and Blood Institute of the National Institutes of Health in Bethesda, Maryland. From 1993-1998 he was a Tenure Track Investigator heading the Section of NMR of the Laboratory of Membrane Biochemistry and Biophysics at the National Institute on Alcohol Abuse and Alcoholism of NIH. He is currently the Chief of the Laboratory of Membrane Biochemistry and Biophysics and the Chief of the Section of NMR in the laboratory. For his achievements in lipid biophysics he received the 2007 Avanti Award in Lipids of the Biophysical Society.
Soubias O, Niu SL, Mitchell DC, Gawrisch K. Lipid-rhodopsin hydrophobic mismatch alters rhodopsin helical content. J Am Chem Soc. 2008;130(37):12465-71.
Krepkiy D, Mihailescu M, Freites JA, Schow EV, Worcester DL, Gawrisch K, Tobias DJ, White SH, Swartz KJ. Structure and hydration of membranes embedded with voltage-sensing domains. Nature. 2009;462(7272):473-9.
Kimura T, Yeliseev AA, Vukoti K, Rhodes SD, Cheng K, Rice KC, Gawrisch K. Recombinant cannabinoid type 2 receptor in liposome model activates g protein in response to anionic lipid constituents. J Biol Chem. 2012;287(6):4076-87.
Teague WE Jr, Soubias O, Petrache H, Fuller N, Hines KG, Rand RP, Gawrisch K. Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function. Faraday Discuss. 2013;161:383-95.
Kimura T, Vukoti K, Lynch DL, Hurst DP, Grossfield A, Pitman MC, Reggio PH, Yeliseev AA, Gawrisch K. Global fold of human cannabinoid type 2 receptor probed by solid-state 13C-, 15N-MAS NMR and molecular dynamics simulations. Proteins. 2014;82(3):452-65.