NEW YORK (Reuters Health) - Scientists have learned that zinc binding plays an important role in the normal folding and function of rhodopsin, a light receptor protein in the eye implicated in retinitis pigmentosa, a hereditary degenerative disease that often leads to blindness.
“Without zinc binding, rhodopsin is very unstable, a feature that is typical of retinitis pigmentosa,” Dr. John Hwa from Dartmouth Medical School in Hanover, New Hampshire, told Reuters Health. “This has implications for therapy for retinitis pigmentosa where zinc concentration in the retina may be important,” he said.
Dr. Hwa and colleagues identified a zinc-binding site within the transmembrane domain of rhodopsin. This zinc coordination site is “critical for normal rhodopsin folding, 11-cis-retinal binding, and the stability of the chromophore-receptor interaction, defects of which are observed in retinitis pigmentosa,” they write in the August 20th issue of the Journal of Biological Chemistry.
The scientists also discovered a cluster of retinitis pigmentosa mutations localized within and around this area where zinc is supposed to bind with rhodopsin.
According to Dr. Hwa, too little zinc in the body or a mutation in a zinc-binding site renders rhodopsin susceptible to misfolding, leading to cell death, degeneration of the retina, and eventually blindness. He acknowledged that his team has “yet to determine what the zinc concentration should be.”
“Based on these studies, we believe that improvement in zinc binding to rhodopsin at this site within the transmembrane domain may be a pharmacological approach for the treatment of select retinitis pigmentosa mutations,” Dr. Hwa and colleagues conclude.
Source: J Biol Chem 2004;279:35932-35941. [ Google search on this article ]
Copyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
