Rao Yi: A potential Nobel Prize in Chemistry
Peking University, May 18, 2011: Professor Rao Yi, dean of PKU School of Life Sciences, casts his sight on a new hotspot in structural biology. In a commentary for his column on Peking University Gazette, Professor Rao regarded G-protein-coupled receptor (GPCR) as a potential Nobel Prize winner. Excerpts follow:
Prof. Rao Yi (PKU School of Life Sciences)
GPCR is a kind of transmembrane protein, which in most cases conducts extracellular signals into the cells.
A sketch map of a typical GPCR molecule on the cell membrane (Vanderbilt University)
The discovery of GPCR has spanned across centuries, since the first case was found on retina in the 19th century. The protein, once called “visual purple” by a German doctor Willy Kühneand, is known as “rhodopsin” now.
Later experiments indicated that rhodopsin is very important to vision. As the first membranin studied by scientists, the discovery of rhodopsin not only aided people's understanding of vision, but also helped later studies and researches on some other membranins. During a long period of time, it was the only membranin studied by a large number of people.
During the 1960s to 1980s, scientists found that G-protein can adjust the receptors of many transmitters and hormones, so those receptors are called GPCR. In 1994, American scientists Alfred Gilman and Martin Rodbell won the Nobel Prize in Physiology or Medicine, for they discovered G-protein and put forward the concept of GPCR.
The Nobel Prizes will be almost definitely given to structural biological researches on rhodopsin or GPCR.
In my opinion, if the Nobel Committee for Chemistry did better, Yoshiaki Kimura – who discovered bacterial rhodopsin in 1997 – should have been awarded in 2003. In fact, the Nobel Prize in Chemistry in 2003 should have been given to MacKinnon – who first resolved the potassium channel protein – and Kimura, instead of the scientist who discovered aquaporin. As soon as the potassium channel protein was resolved, it obtained wide attention - including that from the committee, while rhodopsin wasn’t in fashion then and received little of their attention.
In recent years, the structure of GPCR has become a very hot theme for scientific researches. Therefore, even the committee paid more attention to it and a Nobel Prize in Chemistry can be expected. However, it is not difficult to find out important researches for someone who really spend some time in having a look at the field.
When rhodopsin was not as hot as it is today or before the first GPRC was resolved, few laboratories studied its structures. Now it has become so hot that resolving the structure of a GPRC and publishing a paper can attract a number of readers and quotes, but only the few early researches can be regarded as the real breakthroughs.
In consideration of the need of understanding biological mechanism, structural biology will continue playing an important role in the predictable future, especially the X-ray diffraction structural analysis will continue to be useful. If scientists can do researches on the living structure and dynamic structure of macromolecules and observe their structural changes in vivo in the future, then the generalized structural biology will play a more important role.
Müller R (1851). Zur Histologie der Netzhaut. Z. Wiss. Zool. 3:234-237.
Boll F (1877). Zur Anatomie und Physiologie der Retina. Arch. Anat. Physiol. Physiol. Abt: 4-35.
Ripps H (2008). The color purple: milestones in photochemistry. FASEB J 22:4038-4043.
Kühne W (1879). Chemische Vorgaenge in der Netzhaut. Hermann L. eds. Handbuch d. Physiologie d. Sinnesorgane Erster Theil, Gesichtssinn. F.C.W. Vogel Leipzig, Germany.
Kühne W (1882). Beitraege zur Optochemie. Untersuchungen aus dem physiologischen Institute der Universitaet Heidelberg 4:169-249.
Wolf G (2001). The discovery of the visual function of Vitamin A. J Nutrition 131:1647-1650.
Heller J, Lawrence MA (1970). Structure of the glycopeptide from bovine visual pigment 500. Biochemistry 9:864-869.
Hargrave PA (1977). The amino-terminal tryptic peptide of bovine rhodopsin; a glycopeptide containing two sites of oligosaccharide attachment. Biochim Biophys Acta. 492:83-94.
Hargrave P. A., McDowell J. H., Curtis D. R., Wang J. K., Juszczak E., Fong S. L., Rao J. K., Argos P. (1983). The structure of bovine rhodopsin. Biophys. Struct. Mech. 9:235-244.
Ovchinnikov Iu A., Abdulaev N. G., Feigina M., Artamonov I. D., Bogachuk A. S. (1983). Visual rhodopsin. III. Complete amino acid sequence and topography in a membrane. Bioorg. Khim. 9:1331-1340.
Kimura, Y., Vassylyev, D.G., Miyazawa, A., Kidera, A., Matsushima, M., Mitsuoka, K., Murate, K., Hirai, T. & Fujiyoshi, Y. (1997). Surface of bacteriorhodopsin revealed by high-resolution electron crystallography. Nature 389:206-211.
Belrhali, H., Nollert, P., Royant A., Menzel, C., Rosenbusch, J.P., Landau, E.M. & Pebay-Peyroula, E. (1999). Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrane at 1.9 A resolution. Structure 7:909-917.
Palczewski K, Kumasaka T., Hori T., Behnke C. A., Motoshima H., Fox B. A., Le Trong I., Teller D. C., Okada T., Stenkamp R. E., Yamamoto M., Miyano M. (2000). Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289:739-745.
Rasmussen, S.G.F, Choi, H.J, Rosenbaum, D.M., Kobilka, T.S., Thian, F.S., Edwards, P.C., Burghammer, M., Rratnala, V.R.P, Sanishvili, R. Fischetti, R.F., Schertler, G.F.X, Weis, W.I., Kobilka, B.K (2007). Crystal structure of the human beta 2 adrenergic G protein coupled receptor. Nature 450:383-7.
Rosenbaum, DM, Cherezov V, Hanson MA, Rasmussen SGF, Thian FS, Kolbilka ST, Choi H-J, Yao X-J, Weis WI, Stevens RC, Kolbika BK (2007). GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function. Science 318:1266-1273.
Cherezov V, Rosenbaum, DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK and Stevens RC (2007). High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor Science 318:1258-1265.
Rasmussen, S. G. et al. (2007). Crystal structure of the human β2 adrenergic G-protein-coupled receptor. Nature 450:383-387.
Jaakola, V. P. et al. (2008). The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322:1211-1217.
Shen WL, Kwon L, Adegbola AA, Luo J, Chess A, Montell C (2011). Function of rhodopsin in temperature discrimination in Drosophila. Science 331:1333-1336.
Written by: Xu Xinyi
Edited by: Arthars
Source: Peking University Gazette