Dr. Liebman's laboratory uses physical biochemical approaches to determine the mechanisms that control strength, speed and stability of signaling molecule interactions in hormone, neural and sensory signaling systems with emphasis on receptors, G proteins and membranes. The 7-transmembrane helix receptor (7TMHR) family initiates cell signaling events for thousands of hormones, pheromones and neuro-transmitters plus light, taste and smell stimuli. Each receptor requires a G protein signaling partner.

With a view to understand the molecular mechanics of all such systems, current work of Dr. Liebman's laboratory focuses on the most accessible of these systems, and studies: 1) the molecular coupling mechanism of visual transduction; 2) the mechanism of nucleotide activation of G proteins; 3) G protein ligand-dependent folding stability; 4) 7TMHR conformation, kinetics and stability; 5) the structural basis for receptor-arrestin and G protein recognition and effect of receptor phosphorylation; 6) the role of membrane protein embedding and surface charge in the above; and 7) the mechanism of anesthetic effect on signaling proteins. Specific thermodynamic, kinetic and structure questions and models are investigated through experiments utilizing computational modeling, UV-visible absorption, circular dichroism and tryptophan fluorescence spectroscopy, light scattering, calorimetry and radiotracers which are interpreted in light of static x-ray and NMR structures of the respective native proteins and activity of their misfunctional mutants. Dr. Liebman is the originator and director of Biochem/Biophys 550, Molecular mechanisms of signal transduction and control.

1. R.D. Hamer, S.C. Nicholas, D. Tranchina, P.A. Liebman and T.D. Lamb (2003) Multiple Steps of Phosphorylation of Activated Rhodopsin Can Account for the Reproducibility of Vertebrate Rod Single-photon Responses. The Journal of General Physiology 122:419-444
2. Y.Ishizawa, R.Pidikiti, P.A. Liebman, and R.G. Eckenhoff (2002) G Protein-Coupled Receptors as Direct Targets of Inhaled Anesthetics. Molecular Pharmacology 61:945-952
3. B. Zelent, Y. Veklich, J. Murray, J. H. Parkes, S.K. Gibson, and P. A. Liebman (2001) Rapid Irreversible G Protein Alpha Subunit Misfolding Due to Intramolecular Kinetic Bottleneck that Precedes Mg2+ "Lock" after GTP/GDP Exchange Biochemistry 40:9647-9656
4. J.W. Tanner, J.S. Johansson, P.A. Liebman, and R.G. Eckenhoff (2000) Predictability of Weak Binding from X-ray Crystallography: Inhaled Anesthetics and Myoglobin. Biochemistry 40:5075-5080
5. Gibson, S.K, J.H. Parkes, and P.A. Liebman (2000) Phosporylation Modulates the Affinity of Light-activated Rhodopsin for G Protein and Arrestin. Biochemistry 39:5738-5749
6. Gibson, S.K, J.H. Parkes, and P.A. Liebman (1999) Phosphorylation alters pH-dependent active state equilibrium of rhodopsin by modulating membrane surface potential. Biochemistry 38:11103-11114.
7. Parkes, J.H., S.K. Gibson and P.A. Liebman (1999) Temperature and pH dependence of the metarhodopsin I metarhodopsin II equilibrium and the binding of metarhodopsin II to G protein in rod disk membranes. Biochemistry 38:6862-6878.
8. Tanner, J.W., R.G. Eckenhoff and P.A. Liebman (1999) Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin. Biochim. Biophys. Acta 1430:46-56.
9. Gibson, S.K., J.H. Parkes, and P.A. Liebman (1998) Phosphorylation stabilizes the active conformation of rhodopsin. Biochemistry 37:11393-11398.
   

ROTATION PROJECTS:

1. Titration microcalorimetry of protein-protein bonding energetics.
2. Dynamic light scattering and fluorescence anisotropy of protein-protein interactions.
3. Enzyme activity modulation by membrane curvature stress.
4. Protein misfolding as a general mechanism of biological senescence.
5. Construction of a differential titration photocalorimeter.
6. Effect of osmotic stress on enzymatic activity.
7. Other spectroscopic projects.