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Kinetic Thinking: Back to the Future
Published in Clive R. Bagshaw, Biomolecular Kinetics, 2017
The investigations of Chakrabarti and colleagues [66] on the interaction of recoverin with a rhodopsin kinase peptide provide an excellent example of a multifaceted investigation of a binding mechanism. Recoverin is an E–F hand calcium-binding protein that undergoes a large structural change on binding Ca2+ to expose a binding site between two flanking α-helices [760]. However, on binding the target peptide from rhodopsin kinase [761], the helices undergo further separation (Figure 10.9a). Does this latter movement occur before or after binding the peptide? Chakrabarti and colleagues [66] used NMR spectroscopy to demonstrate the presence of a minor population (2 to 3%) of the apo recoverin protein, which resembled the peptide-bound conformation, and determined the kinetics of exchange with the dominant species at two temperatures. At 30°C, the exchange rate constant (k+0 + k−0) was 1085 ± 100 s−1 and the minor population was 3.2% ± 0.5%, indicating k+0 = 36 s−1. They also performed stopped-flow measurements to follow the binding reaction via recoverin tryptophan fluorescence and showed the limiting observed rate constant at high peptide concentration was similar (32 s−1). This is suggestive of a conformational selection mechanism where at saturating peptide (ligand), the kobs for binding is limited by k+0, as in Equation 10.14.
Neuro-Ophthalmic Literature Review
Published in Neuro-Ophthalmology, 2022
David A. Bellows, John J. Chen, Hui-Chen Cheng, Panitha Jindahra, Peter W. MacIntosh, Collin McClelland, Michael S. Vaphiades, Xiaojun Zhang
Autoantibody against CRX/CORD2, HSP60, and aldolase C were found in higher rates than in patients with RP and normal controls, while α-enolase and CAII were seen at equal rates. Antibodies against recoverin were found in three patients with autoimmune retinopathy, and not seen in normal controls or patients with RP. The area under the receiver operator characteristic curve was 0.531 for anti-recoverin, 0.479 for anti-α-enolase, 0.489 for anti-CAII, 0.737 for anti-CRX/CORD2, 0.637 for anti-HSP60, and 0.664 for anti-aldolase C. A higher number of retinal antibodies was associated with autoimmune retinopathy (≥4 antibodies were seen in 32.6% of patients with autoimmune retinopathy, 5% of patients with RP, and 3% of controls). A higher number of anti-retinal antibodies were slightly associated with photodisruption on optical coherence tomography and severe dysfunction on electroretinography.
Clinical Correlation between Acute Exudative Polymorphous Paraneoplastic Vitelliform Maculopathy and Metastatic Melanoma Disease Activity: A 48-month Longitudinal Case Report
Published in Ocular Immunology and Inflammation, 2022
Claire M Mueller, Sara L Hojjatie, David H Lawson, Nieraj Jain, Joshua Robinson, Mohammad K Khan, Melinda L Yushak, Ghazala A Datoo O’Keefe
Our patient had antiretinal antibodies to the photoreceptor proteins recoverin and transducin- α, and no demonstrable anti-bestrophin 1 antibodies.8 Recoverin is a calcium-binding phototransduction protein whose autoantibodies are associated with cancer-associated retinopathy, characterized by rapid and severe panretinal photoreceptor degeneration.17 Our patient did not demonstrate a typical retinal phenotype or disease course for anti-recoverin associated retinal degeneration. Transducin-α is a phototransduction-involved retinal G-protein whose autoantibodies can lead to retinal degeneration and have been previously reported in MAR.9,18,19 Anti-transducin associated AIR does typically follow a slower, milder course, as in our patient. However, we are not aware of any cases of AEPPVM associated with anti-transducin antibody, and it is unclear if this antibody played a role in the pathogenesis of this patient’s disease. Aside from testing for anti-bestrophin 1 antibodies, we did not perform an assay for other anti-RPE antibodies, therefore it is possible that this patient did have an unidentified anti-RPE antibody.
Non-paraneoplastic related retinopathy: clinical challenges and review
Published in Ophthalmic Genetics, 2019
Júlia T. Takiuti, Vitor K. L. Takahashi, Christine L. Xu, Ruben Jauregui, Stephen H. Tsang
Recoverin is a 23-kDa calcium-binding protein localized in photoreceptors, and although it is most usually specific for CAR, it can also be related to npAIR (7,29,30). This protein is involved in regulating rhodopsin phosphorylation during dark and light adaptation via a calcium-dependent process. Anti-recoverin retinopathy has been associated with various cancers including small-cell lung, uterine sarcoma, cervical and endometrial carcinomas, invasive thymoma, and mixed Mullerian tumors. The clinical phenotype of anti-recoverin-associated CAR is usually aggressive, with severe dysfunction of both rods and cones and significant vision loss (31). In some cases, patients cannot perceive light at all. Adamus et al. demonstrated that peritoneal injection of rat models with recoverin caused photoreceptor cell degeneration and the formation of features associated with uveoretinitis such as photoreceptor cell layer loss, perivasculitis, vitreous cells, and retinal lesions (32).