Papers of the Week| Volume 279, ISSUE 34, e99904, August 20, 2004

Seeing Zinc♦

    Open AccessPublished:August 20, 2004DOI:
        Zinc deficiencies have been linked to both retinal neurodegeneration and night blindness. This association is not surprising given that zinc is an essential component of many proteins, including the photoreceptor rhodopsin. By determining the exact location of zinc in the rhodopsin molecule, Aleksandar Stojanovic and colleagues have shown how zinc deficiency can lead to rhodopsin dysfunction.
        The researchers first looked at the crystal structure of rhodopsin to determine possible locations of zinc ions and then examined these sites for occupancy using inductively coupled plasma mass spectrometry and fluorescent detection of zinc. Stojanovic et al. found that rhodopsin contains a high affinity zinc-specific coordination site within its 11-cis-retinal chromophore binding pocket. Mutagenesis of the three highly conserved amino acids that form the coordination site lowered rhodopsin's affinity for zinc, destabilized the 11-cis-retinal binding pocket, altered spectral properties of the chromophore, and diminished retinal binding. The scientists hypothesize that zinc stabilizes rhodopsin in its inactive ground (dark) state and that photoactivation disrupts zinc coordination leading to structural changes and the formation of photoactivated intermediates. Because a cluster of retinitis pigmentosa mutations localize within and around the zinc binding site, the authors believe that certain forms of this degenerative eye disease may eventually be treated by improving zinc binding to rhodopsin.
        Figure thumbnail gr1
        Locations of putative zinc coordination sites on rhodopsin.