Professor Hee‑Wook Choi, Department of Chemistry, Jeonbuk National University (JBNU), has attracted global academic attention by being the first in the world to identify various visual signal‑transmitting molecules and structures in the eye that enable vision.

Professor Choi published in the latest issue of Nature (doi:10.1038/nature12133) the world’s first structure showing how the biomolecule arrestin, present in the eye, becomes activated upon encountering metarhodopsin II and binds to metarhodopsin II. Until now, only inactive (nonfunctional) structures of arrestin had been known. With this publication, Professor Choi has achieved a remarkable sixth Nature paper during his tenure at JBNU, all in the field of visual signal transduction.

Previously, Professor Choi has published successive papers in the leading journal Nature elucidating the roles and structures of the biomolecules opsin and rhodopsin, which enable the eye to detect light, and the structure of metarhodopsin II, the light‑activated form of rhodopsin.

When light enters the eye, the biomolecule rhodopsin in the eye detects it. The light‑activated rhodopsin then changes its conformation to metarhodopsin II. Metarhodopsin II activates G proteins, which transmit extracellular chemical signals into the cell and relay visual signals to the brain, enabling vision.

Put simply, even as we are seeing, the eye undergoes a rapid, continuous cycle of rhodopsin → metarhodopsin II → rhodopsin → metarhodopsin II ….

In this process, metarhodopsin II activates G proteins to transmit visual signals to the brain, but must then promptly deactivate the G proteins and rapidly revert to rhodopsin. Arrestin is the molecule that restores the G proteins to their inactive state.

If arrestin fails to bind to metarhodopsin II and inactivate the G proteins, the same visual signal would continue to be transmitted to the brain. In other words, a flash of light would still be perceived by the brain as continuous illumination.

This study provides the basis for explaining how arrestin binds to activated metarhodopsin II to terminate visual signal transmission and how the molecule is then regenerated back to rhodopsin.

This research was achieved through more than two years of strenuous effort by Professor Choi and his mentee, Researcher Yong‑Joo Kim (Institute of Medical Physics and Biophysics, Humboldt University, Germany; JBNU, Department of Chemistry, Class of 1995). Professor Choi previously published the structure of inactive arrestin in Nature in 1998, published two papers in 2008, and in 2011 reported the structure of metarhodopsin II in Nature. With this new Nature publication, he has further established himself as a world‑leading scholar in visual signal transduction research.

Notably, Professor Choi's paper was published back‑to‑back with a paper by the research team of Robert J. Lefkowitz and Brian K. Kobilka—recipients of the 2012 Nobel Prize in Chemistry—on the complex structure of a phosphorylated V2 vasopressin receptor peptide (V2Rpp, 29 residues) bound to β‑arrestin and antibody Fab30.

The two papers present crystallographic and structural analyses of arrestin in different activation states, attracting significant attention from the global academic community. Professor G. Bueldt's commentary on the two papers is given prominent coverage in the "News and Views" section of the same issue of Nature.

Professor Choi said, "This study establishes the first foundation for explaining how arrestin, previously known only in its inactive form, becomes activated upon encountering metarhodopsin II, thereby stopping visual signal transmission and allowing rhodopsin to be regenerated." He added, "Elucidating the structures of the biomolecules that mediate visual signal transmission one after another is expected to greatly aid the prevention and treatment of severe congenital and acquired ophthalmic diseases such as Oguchi disease and Stargardt disease."

This research was financially supported by a Basic Science Program general research project funded by the National Research Foundation (NRF) of the Ministry of Education, Science and Technology, which Professor Choi is conducting.