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| | <StructureSection load='6qba' size='340' side='right'caption='[[6qba]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='6qba' size='340' side='right'caption='[[6qba]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qba]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_35091 Atcc 35091] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QBA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QBA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qba]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_35091 Atcc 35091] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QBA FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2T1:2-[({4-[2-(TRIFLUOROMETHYL)PHENYL]PIPERIDIN-1-YL}CARBONYL)AMINO]BENZOIC+ACID'>2T1</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2T1:2-[({4-[2-(TRIFLUOROMETHYL)PHENYL]PIPERIDIN-1-YL}CARBONYL)AMINO]BENZOIC+ACID'>2T1</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RBP4, PRO2222 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), sso7a1, sso7d-2, SSO9180, sso7a2, sso7d-3, SSO9535 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2287 ATCC 35091])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RBP4, PRO2222 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), sso7a1, sso7d-2, SSO9180, sso7a2, sso7d-3, SSO9535 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2287 ATCC 35091])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qba OCA], [http://pdbe.org/6qba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qba RCSB], [http://www.ebi.ac.uk/pdbsum/6qba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qba 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=6qba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qba OCA], [https://pdbe.org/6qba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qba RCSB], [https://www.ebi.ac.uk/pdbsum/6qba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qba ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN]] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:[http://omim.org/entry/180250 180250]]. This condition causes night vision problems. It produces a typical 'fundus xerophthalmicus', featuring a progressed atrophy of the retinal pigment epithelium. | + | [[https://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN]] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:[https://omim.org/entry/180250 180250]]. This condition causes night vision problems. It produces a typical 'fundus xerophthalmicus', featuring a progressed atrophy of the retinal pigment epithelium. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN]] Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli. | + | [[https://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN]] Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Structural highlights
6qba is a 2 chain structure with sequence from Atcc 35091 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | RBP4, PRO2222 (HUMAN), sso7a1, sso7d-2, SSO9180, sso7a2, sso7d-3, SSO9535 (ATCC 35091) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[RET4_HUMAN] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:180250]. This condition causes night vision problems. It produces a typical 'fundus xerophthalmicus', featuring a progressed atrophy of the retinal pigment epithelium.
Function
[RET4_HUMAN] Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.
Publication Abstract from PubMed
Molecular ON-switches in which a chemical compound induces protein-protein interactions can allow cellular function to be controlled with small molecules. ON-switches based on clinically applicable compounds and human proteins would greatly facilitate their therapeutic use. Here, we developed an ON-switch system in which the human retinol binding protein 4 (hRBP4) of the lipocalin family interacts with engineered hRBP4 binders in a small molecule-dependent manner. Two different protein scaffolds were engineered to bind to hRBP4 when loaded with the orally available small molecule A1120. The crystal structure of an assembled ON-switch shows that the engineered binder specifically recognizes the conformational changes induced by A1120 in two loop regions of hRBP4. We demonstrate that this conformation-specific ON-switch is highly dependent on the presence of A1120, as demonstrated by an approximately 500-fold increase in affinity upon addition of the small molecule drug. Furthermore, the ON-switch successfully regulated the activity of primary human CAR T cells in vitro. We anticipate that lipocalin-based ON-switches have the potential to be broadly applied for the safe pharmacological control of cellular therapeutics.
A conformation-specific ON-switch for controlling CAR T cells with an orally available drug.,Zajc CU, Dobersberger M, Schaffner I, Mlynek G, Puhringer D, Salzer B, Djinovic-Carugo K, Steinberger P, De Sousa Linhares A, Yang NJ, Obinger C, Holter W, Traxlmayr MW, Lehner M Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):14926-14935. doi:, 10.1073/pnas.1911154117. Epub 2020 Jun 17. PMID:32554495[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zajc CU, Dobersberger M, Schaffner I, Mlynek G, Puhringer D, Salzer B, Djinovic-Carugo K, Steinberger P, De Sousa Linhares A, Yang NJ, Obinger C, Holter W, Traxlmayr MW, Lehner M. A conformation-specific ON-switch for controlling CAR T cells with an orally available drug. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):14926-14935. doi:, 10.1073/pnas.1911154117. Epub 2020 Jun 17. PMID:32554495 doi:http://dx.doi.org/10.1073/pnas.1911154117
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