Crystal structure of native RPE65, the retinoid isomerase of the visual cycle

Journal Article · Tue Dec 01 04:00:00 EST 2009 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.0906600106· OSTI ID:1005985

Kiser, Philip D; Golczak, Marcin; Lodowski, David T; Chance, Mark R; Palczewski, Krzysztof

Vertebrate vision is maintained by the retinoid (visual) cycle, a complex enzymatic pathway that operates in the retina to regenerate the visual chromophore, 11-cis-retinal. A key enzyme in this pathway is the microsomal membrane protein RPE65. This enzyme catalyzes the conversion of all-trans-retinyl esters to 11-cis-retinol in the retinal pigment epithelium (RPE). Mutations in RPE65 are known to be responsible for a subset of cases of the most common form of childhood blindness, Leber congenital amaurosis (LCA). Although retinoid isomerase activity has been attributed to RPE65, its catalytic mechanism remains a matter of debate. Also, the manner in which RPE65 binds to membranes and extracts retinoid substrates is unclear. To gain insight into these questions, we determined the crystal structure of native bovine RPE65 at 2.14-{angstrom} resolution. The structural, biophysical, and biochemical data presented here provide the framework needed for an in-depth understanding of the mechanism of catalytic isomerization and membrane association, in addition to the role mutations that cause LCA have in disrupting protein function.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005985
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (41) ; 10, 2009 Vol. 106; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CATTLE
CRYSTAL STRUCTURE
ENZYMES
EPITHELIUM
ESTERS
ISOMERASES
ISOMERIZATION
MEMBRANE PROTEINS
MEMBRANES
MUTATIONS
PROTEINS
RESOLUTION
RETINA
RHODOPSIN
SUBSTRATES
VERTEBRATES
VISION