Interphotoreceptor retinoid-binding protein (IRBP), which is secreted by photoreceptors into the interphotoreceptor matrix, is a candidate for retinal degenerations. In the matrix, IRBP has access to Muller cell villi, outer segments, and apical RPE. Mata et al. proposed that IRBP carries 11-cis and all-trans retinol between the Muller cells and cone outer segments. However, this role, or another function is poorly understood because little is known about the structure of IRBP. Our long term goal is to define the relationship between the structure and function of IRBP. IRBP consists of homologous """"""""modules"""""""" (4 in tetrapods and 2 in teleost fish). Each module is about 300 residues in length, and binds 1 to 2 molecules of retinoid or fatty acid. The X-ray crystal structure of an individual module shows: 1) a hydrophobic betabetaalpha-spiral fold, and 2) a solvent exposed surface domain containing highly conserved basic residues. Our Hypothesis is: the betabetaalpha fold forms the retinoid-binding site, and the surface domain allows IRBP to interact with the matrix and or outer segment. This will be evaluated through the following complementary Specific Aims.
Aim #1 : To determine if the betabetaalpha-spiral fold is IRBP's hydrophobic ligand-binding domain, and whether it can discriminate between 11-cis and all-trans retinol.
Aim #2 : To determine whether the conserved surface domain: 1) binds glycosaminoglycans particularly hyaluronan, and/or 2) facilitates the release or delivery of retinoids at the outer segment.
Aim #3 : To determine the X-ray crystal structure of the IRBP-ligand complex, and the full-length native bovine IRBP and zebrafish IRBP.
| Gonzalez-Fernandez, Federico; Fornalik, Mark; Garlipp, Mary Alice et al. (2018) Pericellular interphotoreceptor matrix dictates outer retina critical surface tension. Exp Eye Res 167:163-173 |
| Chen, Chunhe; Adler 4th, Leopold; Goletz, Patrice et al. (2017) Interphotoreceptor retinoid-binding protein removes all-trans-retinol and retinal from rod outer segments, preventing lipofuscin precursor formation. J Biol Chem 292:19356-19365 |
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| Ghosh, Debashis; Haswell, Karen M; Sprada, Molly et al. (2016) Fold conservation and proteolysis in zebrafish IRBP structure: Clues to possible enzymatic function? Exp Eye Res 147:78-84 |
| Patel, Sangita P; Schaefer, Jamie L; Jaber, Ryan et al. (2016) The Value of Cytology Smears for Acanthamoeba Keratitis. Case Rep Ophthalmol Med 2016:4148968 |
| Gonzalez-Fernandez, Federico; Betts-Obregon, Brandi; Tsin, Andrew T et al. (2016) Technical brief: Pump-probe paradigm in an integrating cavity to study photodecomposition processes. Mol Vis 22:953-8 |
| Ghosh, Debashis; Haswell, Karen M; Sprada, Molly et al. (2015) Structure of zebrafish IRBP reveals fatty acid binding. Exp Eye Res 140:149-158 |
| Gonzalez-Fernandez, Federico; Betts-Obregon, Brandi; Yust, Brian et al. (2015) Interphotoreceptor retinoid-binding protein protects retinoids from photodegradation. Photochem Photobiol 91:371-8 |
| Gonzalez-Fernandez, Federico; Sung, Dongjin; Haswell, Karen M et al. (2014) Thiol-dependent antioxidant activity of interphotoreceptor retinoid-binding protein. Exp Eye Res 120:167-74 |
| Sane, M; Selvadurai, A; Reidy, J et al. (2014) Transient visual loss due to reversible 'pending' central retinal artery occlusion in occult giant cell arteritis. Eye (Lond) 28:1387-90 |
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