Impact of retinal disease-associated RPE65 mutations on retinoid isomerization.

Biochemistry
Grzegorz BeretaKrzysztof Palczewski

Abstract

Pathogenic mutations in the RPE65 gene are associated with a spectrum of congenital blinding diseases in humans. We evaluated changes in the promoter region, coding regions, and exon/intron junctions of the RPE65 gene by direct sequencing of DNA from 36 patients affected with Leber's congenital amaurosis (LCA), 62 with autosomal recessive retinitis pigmentosa (arRP), and 21 with autosomal dominant/recessive cone-rod dystrophies (CORD). Fifteen different variants were found, of which 6 were novel. Interesting was Gly244Val, a novel mutation close to the catalytic center. To assess the role of this mutation in RPE65 inactivation, we performed detailed biochemical studies of the mutant along with a structural analysis of the 244 amino acid position with respect to amino acids known to be important for RPE65-dependent retinoid isomerization. Bicistronic plasmid expression of the RPE65 Gly244Val mutant and enhanced green fluorescent protein (EGFP) allowed us to document both its instability in cultured cells by cell sorting and immunoblotting methodology and its loss of RPE65-dependent isomerase activity by enzymatic assays. Further insights into the structural requirements for retinoid isomerization by RPE65 were obtained by using ...Continue Reading

References

Jan 22, 1982·Nucleic Acids Research·S M Mount
Jun 20, 1997·Science·S H SchwartzD R McCarty
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·H MorimuraT P Dryja
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Apr 15, 2000·Archives of Ophthalmology·A J LoteryE M Stone
May 20, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·M DancigerD B Farber
Jun 28, 2000·Proceedings of the National Academy of Sciences of the United States of America·J P Van HooserK Palczewski
Apr 28, 2001·Nature Genetics·G M AclandJ Bennett
May 22, 2001·Archives of Biochemistry and Biophysics·J von Lintig, A Wyss
Mar 19, 2002·The Journal of Biological Chemistry·J Preston Van HooserKrzysztof Palczewski
Oct 31, 2003·Experimental Hematology·Toshio KitamuraHidetoshi Kumagai
Aug 24, 2004·American Journal of Human Genetics·Isabelle PerraultJean-Michel Rozet
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Feb 5, 2005·Ophthalmology·Jennifer A GalvinRobert K Koenekoop
Apr 12, 2005·Science·Daniel P KloerGeorg E Schulz
Aug 13, 2005·Cell·Minghao JinGabriel H Travis
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gennadiy MoiseyevJian-Xing Ma
Sep 10, 2005·Proceedings of the National Academy of Sciences of the United States of America·T Michael RedmondSusan Gentleman
Oct 6, 2005·Retina·Jennifer A GalvinRobert K Koenekoop
Oct 18, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gregory M AclandSamuel G Jacobson
Mar 7, 2006·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Leila El MatriFrancis L Munier
Jun 8, 2006·Annual Review of Biochemistry·Krzysztof Palczewski
Sep 14, 2006·Annual Review of Pharmacology and Toxicology·Gabriel H TravisKrzysztof Palczewski
Oct 3, 2006·American Journal of Ophthalmology·Audrey SénéchalChristian P Hamel
Jan 2, 2007·Investigative Ophthalmology & Visual Science·Samuel G JacobsonDebra A Thompson
Aug 30, 2007·Nature Reviews. Genetics·Guey-Shin Wang, Thomas A Cooper
Sep 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Samuel G JacobsonKrzysztof Palczewski
Jan 16, 2008·The Journal of Biological Chemistry·Marcin GolczakKrzysztof Palczewski
Apr 29, 2008·The New England Journal of Medicine·Albert M MaguireJean Bennett
Apr 29, 2008·The New England Journal of Medicine·James W B BainbridgeRobin R Ali

❮ Previous
Next ❯

Citations

Jul 6, 2013·Archives of Biochemistry and Biophysics·Xuewu SuiKrzysztof Palczewski
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Philip D KiserKrzysztof Palczewski
Jan 27, 2010·The Journal of Biological Chemistry·Marcin GolczakKrzysztof Palczewski
Sep 26, 2013·PloS One·Anshuman VermaPeriasamy Sundaresan
Apr 20, 2010·Progress in Retinal and Eye Research·Artur V Cideciyan
May 12, 2009·Human Mutation·A R PhilpEdwin M Stone
Jul 16, 2010·The Journal of Biological Chemistry·Lakshmi Padmavathi Pulagam, Krzysztof Palczewski
Sep 8, 2021·Experimental Eye Research·Rosario Lopez-RodriguezCarmen Ayuso

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.