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Go to research details of CBB faculty:
Prof. Rabi Ann Musah
Prof. Li Niu
Prof. Ramaswamy H. Sarma
Prof. Charles Scholes

Rhodopsin, like all other GPCRs, has seven transmembrane helices connected by three intracellular and three extracellular loops. Rhodopsin kinase phosphorylates the C-terminal tail of rhodopsin, which initiates the termination reaction pathway in visual signal transduction.

Li Niu Laboratory

Assistant Professor of Chemistry, Ph.D., University of Wisconsin (1991), Postdoctoral fellow: Cornell (1991-1997), MIT (1997-2000)
ph: 518-442-4447; fx: 518-452-3462; email:

Understanding how cell surface proteins mediate signal transduction is our primary research interest. In particular, we are interested in the structure and function relationship, and the kinetic and molecular mechanism of regulation of protein function by protein-protein and protein-drug interactions.The activity of virtually every cell is regulated by extracellular signals, such as neurotransmitters, hormones, and sensory stimuli. These signals are transmitted into the cell interior via cell surface receptor proteins.

The first area of our research is to understand how rhodopsin kinase phosphorylates rhodopsin. Rhodopsin is a photoreceptor in the rod cell of vertebrate retina. It is a prototypic member of G-protein coupled receptor family (GPCR), the largest family known of cell surface proteins. Upon light excitation, rhodopsin adopts a conformation that specifically allows binding of transducin, a G-protein. This protein-protein interaction ensures a signal, as weak as a single photon, to be amplified. Binding of rhodopsin kinase and subsequent phosphorylation of rhodopsin, however, initiate signal quenching. Phosphorylation is therefore an essential chemical reaction that regulates signal transduction. Failure to terminate rhodopsin-mediated reaction pathway is known to cause photoreceptor cell death.  Interestingly, rhodopsin kinase seems to exhibit a unique catalytic property in that the kinase is first activated by interacting with the light-activated rhodopsin before it can phosphorylate the rhodopsin. This testable mechanism has been proposed as a general model of regulating GPCR-mediated signal transduction for G-protein receptor kinase family. On the other hand, the structure and function of rhodopsin in the context of its interaction with rhodopsin kinase will also be investigated.  For instance, there are seven putative phosphorylation sites all located in the C-terminal tail of rhodopsin. The number of the sites that must be phosphorylated and the sequence of the phosphorylation among those sites are not yet clear. We are using transient chemical kinetic techniques, site-directed mutagenesis, optical sensor technology based upon surface plasmon resonance, and MALDI-MS in our studies. Our goal is to quantitatively understand how the receptor-mediated reaction is regulated by phosphorylation, and ultimately to determine if a universal mechanism is involved in regulation of the GPCR-mediated signal transduction.

The second area of our research concerns the structure and function of glutamate receptors and the mechanism of drug-receptor interaction. Rapid neuronal signal transmission in the mammalian brain is mediated mostly by ion channel glutamate receptors. The function of glutamate receptors is central to the brain activity, such as memory and learning. Inhibitors of glutamate receptors are promising to treat neurological disorders such as stroke. The glutamate receptor, upon binding to glutamate, a neurotransmitter, rapidly changes its conformation and opens the ion channel pore to allow small ions such as sodium ions to flow across cellular membrane, thus transmitting an electrical signal between neurons. Because the receptor functions even in the ms time region (i.e., the channel opens in the ms time scale, and closes or desensitizes in the ms time domain), a rapid kinetic technique must be used that not only has the sufficient time resolution but also is suitable for study of receptors embedded in cell membrane. The kinetic technique we are using, which meets the criteria above, involves laser-pulse photolysis of caged glutamate and patch clamping. We are currently characterizing:

  1. the chemical kinetic mechanism of channel opening,
  2. the structure and function relationship for this receptor family, together with the use of structural modeling and site-directed mutagenesis, and
  3. how drugs modify the receptor function.

Ultimately, our goal is to understand the correlation of the unique structural features of this receptor family to their function, and to provide mechanistic information for rational design of the drugs that specifically target to new and distinct reaction steps.

Selected Publications

  1. Niu, L., & Hess, G. P. (1993) Biochemistry 32, 3831-3835. An Acetylcholine Receptor Regulatory Site in BC3H1 cells: Characterization by Laser-pulse Photolysis in the Microsecond-to-millisecond Time Domain
  2. Ramesh, D., Wieboldt, R., Niu, L., Carpenter, B. K., & Hess, G. P. (1993) Proc. Natl. Acad. Sci. USA 90, 11074-11078. Photolysis of a New Protecting Group for the Carboxyl Function of Neurotransmitters within 3 µs and with Product Quantum Yield of 0.2
  3. Wieboldt, R., Gee, K. R., Niu, L., Ramesh, D., Carpenter, B. K., & Hess, G. P. (1994) Proc. Natl. Acad. Sci. USA 91, 8752-8756. Photolabile Precursors of Glutamate: Synthesis, Photochemical Properties and Activation of Glutamate Receptors on a Microsecond Time Scale
  4. Niu, L., Abood, L. G., & Hess, G. P. (1995) Proc. Natl. Acad. Sci. USA 92, 12008-12012. Cocaine: Mechanism of Inhibition of a Muscle Acetylcholine Receptor Studied by Laser-pulse Photolysis Technique
  5. Hess, G. P., Niu, L., & Wieboldt, R. (1995) In Annals New York Acad. Sci. 757, 23-39. Determination of the Chemical Mechanism of Neurotransmitter Receptor-mediated Reactions by Rapid Chemical Kinetic Methods
  6. Gee, K. R., Niu, L., Schaper, K., & Hess, G. P. (1995) J. Org. Chemistry 60, 4260-4263. Caged Bioactive Carboxylates. Synthesis, Photolysis Studies, and Biological Characterization of a New Caged N-methyl-D-Aspartate Acid (NMDA)
  7. Niu, L., Gee, K. R., Schaper, K., & Hess, G. P. (1996) Biochemistry 35, 2030-3036. Synthesis and Photochemical Properties of a Kainate Precursor, and Activation of Kainate and AMPA Receptor-channels on a Microsecond Time Scale
  8. Niu, L., Grewer, C., & Hess, G. P. (1996) In Techniques in Protein Chemistry VII (Marshak, D. R., Ed.) pp 139-149, Academic Press, San Diego. Chemical Kinetic Investigations of Neurotransmitter Receptors on a Cell Surface in a µs Time Region
  9. Niu, L., Wieboldt, R., Ramesh, D., Carpenter, B. K., & Hess, G. P. (1996) Biochemistry 35, 8136-8142. Synthesis and Characterization of a Caged Receptor Ligand Suitable for Chemical Kinetic Investigations of the Glycine Receptor in the 3 µs Time Domain
  10. Niu, L., Vazquez, R. W., Nagel, G., Friedrich, T., Bamberg, E., Oswald, R. E., & Hess, G. P. (1996) Proc. Natl. Acad. Sci. USA 93, 12964-12968 Rapid Chemical Kinetic Techniques for Investigations of Neurotransmitter Receptors Expressed in Xenopus Oocytes
  11. Gee, K. R., Niu, L., Schaper, K., Jayaraman, V. & Hess, G. P. (1999) Biochemistry 38, 3140-3147. Synthesis and Photochemistry of a Photolabile Precursor of N-Methyl-D-Aspartate (NMDA) That Is Photolyzed in the Microsecond Time Region and Is Suitable for Chemical Kinetic Investigations of the NMDA receptor
  12. Bruel, C., Cha, K., Niu, L., Khorana, H. G. (2000) Proc. Natl. Acad. Sci. USA 97, 3010-3015. Rhodopsin Kinase: Two mAbs Binding Near the Carboxyl Terminus Cause Time-dependent Inactivation
  13. Hess, G. P., Ulrich, A. H., Bretinger, H.-G., Niu, L., Armanda, G., Grewer, C., Ippolito, J. E., Lee, S., Jayaraman, V., Srivastava, S., & Coombs, S. E. (2000) Proc. Natl. Acad. Sci. USA, in press Mechanism-based Discovery of Ligands that Prevent Inhibition of the Nicotinic Acetylchoine Receptor by Cocaine and MK-801
  14. Niu, L., & Khorana, H. G. (2000) prepared for Proc. Natl. Acad. Sci. USA. Structure and Function Study of Rhodopsin: Asymmetric Reconstitution of Rhodopsin in Liposomes
  15. Niu, L., & Khorana, H. G. (2000) prepared for Proc. Natl. Acad. Sci. USA. Structure and Function Study of Rhodopsin: Molecular Recognition between Rhodopsin and Transducin Characterized Using Surface Plasmon Resonance Spectroscopy
  16. Niu, L. (2000) Prepared for Biochemistry. Dynamics of the C-terminus of Rhodopsin in the Dark, Light, and Opsin States
To detailed reserch projects in Sarma laboratory

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Prof. Li Niu, CBB, Department of Chemistry, The University at Albany
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