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| | ==Crystal structure of bovine RPE65 at 1.9 angstrom resolution== | | ==Crystal structure of bovine RPE65 at 1.9 angstrom resolution== |
| - | <StructureSection load='3kvc' size='340' side='right' caption='[[3kvc]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3kvc' size='340' side='right'caption='[[3kvc]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kvc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KVC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KVC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kvc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KVC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fsn|3fsn]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kvc OCA], [http://pdbe.org/3kvc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kvc RCSB], [http://www.ebi.ac.uk/pdbsum/3kvc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kvc ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kvc OCA], [https://pdbe.org/3kvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kvc RCSB], [https://www.ebi.ac.uk/pdbsum/3kvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kvc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RPE65_BOVIN RPE65_BOVIN]] Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT. The enzymatic activity is linearly dependent of the expression levels and membrane association.<ref>PMID:16096063</ref> <ref>PMID:19805034</ref> <ref>PMID:20100834</ref> | + | [https://www.uniprot.org/uniprot/RPE65_BOVIN RPE65_BOVIN] Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT. The enzymatic activity is linearly dependent of the expression levels and membrane association.<ref>PMID:16096063</ref> <ref>PMID:19805034</ref> <ref>PMID:20100834</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/3kvc_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/3kvc_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3kvc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3kvc" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Retinoid isomerohydrolase|Retinoid isomerohydrolase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Golczak, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Kiser, P D]] | + | [[Category: Golczak M]] |
| - | [[Category: Lodowski, D T]] | + | [[Category: Kiser PD]] |
| - | [[Category: Palczewski, K]] | + | [[Category: Lodowski DT]] |
| - | [[Category: 7-bladed beta-propeller]] | + | [[Category: Palczewski K]] |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Iron]]
| + | |
| - | [[Category: Isomerase]]
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| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Monotopic membrane protein]]
| + | |
| - | [[Category: Non-heme iron protein]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Sensory transduction]]
| + | |
| - | [[Category: Vision]]
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| Structural highlights
Function
RPE65_BOVIN Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT. The enzymatic activity is linearly dependent of the expression levels and membrane association.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Regeneration of visual chromophore in the vertebrate visual cycle involves the retinal pigment epithelium-specific protein RPE65, the key enzyme catalyzing the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol. Although RPE65 has no predicted membrane spanning domains, this protein predominantly associates with microsomal fractions isolated from bovine retinal pigment epithelium (RPE). We have re-examined the nature of RPE65 interactions with native microsomal membranes by using extraction and phase separation experiments. We observe that hydrophobic interactions are the dominant forces that promote RPE65 association with these membranes. These results are consistent with the crystallographic model of RPE65, which features a large lipophilic surface that surrounds the entrance to the catalytic site of this enzyme and likely interacts with the hydrophobic core of the endoplasmic reticulum membrane. Moreover, we report a critical role for phospholipid membranes in preserving the retinoid isomerization activity and physical properties of RPE65. Isomerase activity measured in bovine RPE was highly sensitive to phospholipase A(2) treatment, but the observed decline in 11-cis-retinol production did not directly reflect inhibition by products of lipid hydrolysis. Instead, a direct correlation between the kinetics of phospholipid hydrolysis and retinoid isomerization suggests that the lipid membrane structure is critical for RPE65 enzymatic activity. We also provide evidence that RPE65 operates in a multiprotein complex with retinol dehydrogenase 5 and retinal G protein-coupled receptor in RPE microsomes. Modifications in the phospholipid environment affecting interactions with these protein components may be responsible for the alterations in retinoid metabolism observed in phospholipid-depleted RPE microsomes. Thus, our results indicate that the enzymatic activity of native RPE65 strongly depends on its membrane binding and phospholipid environment.
Importance of membrane structural integrity for RPE65 retinoid isomerization activity.,Golczak M, Kiser PD, Lodowski DT, Maeda A, Palczewski K J Biol Chem. 2010 Mar 26;285(13):9667-82. Epub 2010 Jan 25. PMID:20100834[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jin M, Li S, Moghrabi WN, Sun H, Travis GH. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell. 2005 Aug 12;122(3):449-59. PMID:16096063 doi:10.1016/j.cell.2005.06.042
- ↑ Kiser PD, Golczak M, Lodowski DT, Chance MR, Palczewski K. Crystal structure of native RPE65, the retinoid isomerase of the visual cycle. Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17325-30. Epub 2009 Oct 5. PMID:19805034
- ↑ Golczak M, Kiser PD, Lodowski DT, Maeda A, Palczewski K. Importance of membrane structural integrity for RPE65 retinoid isomerization activity. J Biol Chem. 2010 Mar 26;285(13):9667-82. Epub 2010 Jan 25. PMID:20100834 doi:10.1074/jbc.M109.063941
- ↑ Golczak M, Kiser PD, Lodowski DT, Maeda A, Palczewski K. Importance of membrane structural integrity for RPE65 retinoid isomerization activity. J Biol Chem. 2010 Mar 26;285(13):9667-82. Epub 2010 Jan 25. PMID:20100834 doi:10.1074/jbc.M109.063941
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