7mwn: Difference between revisions

Revision as of 10:17, 14 December 2022

An engineered PYL2-based WIN 55,212-2 synthetic cannabinoid sensor with a stabilized HAB1 variant

Structural highlights

7mwn is a 2 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ACT, CL, GOL, MG, PEG, WI5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PYL2_ARATH Receptor for abscisic acid (ABA) required for ABA-mediated responses such as stomatal closure and germination inhibition. Inhibits the activity of group-A protein phosphatases type 2C (PP2Cs) when activated by ABA.^[1] ^[2]

Publication Abstract from PubMed

A general method to generate biosensors for user-defined molecules could provide detection tools for a wide range of biological applications. Here, we describe an approach for the rapid engineering of biosensors using PYR1 (Pyrabactin Resistance 1), a plant abscisic acid (ABA) receptor with a malleable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which facilitates the construction of sense-response functions. We applied this platform to evolve 21 sensors with nanomolar to micromolar sensitivities for a range of small molecules, including structurally diverse natural and synthetic cannabinoids and several organophosphates. X-ray crystallography analysis revealed the mechanistic basis for new ligand recognition by an evolved cannabinoid receptor. We demonstrate that PYR1-derived receptors are readily ported to various ligand-responsive outputs, including enzyme-linked immunosorbent assay (ELISA)-like assays, luminescence by protein-fragment complementation and transcriptional circuits, all with picomolar to nanomolar sensitivity. PYR1 provides a scaffold for rapidly evolving new biosensors for diverse sense-response applications.

Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds.,Beltran J, Steiner PJ, Bedewitz M, Wei S, Peterson FC, Li Z, Hughes BE, Hartley Z, Robertson NR, Medina-Cucurella AV, Baumer ZT, Leonard AC, Park SY, Volkman BF, Nusinow DA, Zhong W, Wheeldon I, Cutler SR, Whitehead TA Nat Biotechnol. 2022 Jun 20. doi: 10.1038/s41587-022-01364-5. PMID:35726092^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Melcher K, Ng LM, Zhou XE, Soon FF, Xu Y, Suino-Powell KM, Park SY, Weiner JJ, Fujii H, Chinnusamy V, Kovach A, Li J, Wang Y, Li J, Peterson FC, Jensen DR, Yong EL, Volkman BF, Cutler SR, Zhu JK, Xu HE. A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors. Nature. 2009 Dec 3;462(7273):602-8. PMID:19898420 doi:10.1038/nature08613
↑ Yin P, Fan H, Hao Q, Yuan X, Wu D, Pang Y, Yan C, Li W, Wang J, Yan N. Structural insights into the mechanism of abscisic acid signaling by PYL proteins. Nat Struct Mol Biol. 2009 Dec;16(12):1230-6. Epub 2009 Nov 5. PMID:19893533 doi:10.1038/nsmb.1730
↑ Beltran J, Steiner PJ, Bedewitz M, Wei S, Peterson FC, Li Z, Hughes BE, Hartley Z, Robertson NR, Medina-Cucurella AV, Baumer ZT, Leonard AC, Park SY, Volkman BF, Nusinow DA, Zhong W, Wheeldon I, Cutler SR, Whitehead TA. Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds. Nat Biotechnol. 2022 Jun 20. doi: 10.1038/s41587-022-01364-5. PMID:35726092 doi:https://dx.doi.org/10.1038/s41587-022-01364-5

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Melcher K, Ng LM, Zhou XE, Soon FF, Xu Y, Suino-Powell KM, Park SY, Weiner JJ, Fujii H, Chinnusamy V, Kovach A, Li J, Wang Y, Li J, Peterson FC, Jensen DR, Yong EL, Volkman BF, Cutler SR, Zhu JK, Xu HE. A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors. Nature. 2009 Dec 3;462(7273):602-8. PMID:19898420 doi:10.1038/nature08613

[2] Yin P, Fan H, Hao Q, Yuan X, Wu D, Pang Y, Yan C, Li W, Wang J, Yan N. Structural insights into the mechanism of abscisic acid signaling by PYL proteins. Nat Struct Mol Biol. 2009 Dec;16(12):1230-6. Epub 2009 Nov 5. PMID:19893533 doi:10.1038/nsmb.1730

[3] Beltran J, Steiner PJ, Bedewitz M, Wei S, Peterson FC, Li Z, Hughes BE, Hartley Z, Robertson NR, Medina-Cucurella AV, Baumer ZT, Leonard AC, Park SY, Volkman BF, Nusinow DA, Zhong W, Wheeldon I, Cutler SR, Whitehead TA. Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds. Nat Biotechnol. 2022 Jun 20. doi: 10.1038/s41587-022-01364-5. PMID:35726092 doi:https://dx.doi.org/10.1038/s41587-022-01364-5

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7mwn is ON HOLD  until Paper Publication
+==An engineered PYL2-based WIN 55,212-2 synthetic cannabinoid sensor with a stabilized HAB1 variant==
+<StructureSection load='7mwn' size='340' side='right'caption='[[7mwn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7mwn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MWN FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=WI5:{(3R)-5-methyl-3-[(morpholin-4-yl)methyl]-2,3-dihydro[1,4]oxazino[2,3,4-hi]indol-6-yl}(naphthalen-1-yl)methanone'>WI5</scene></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=7mwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mwn OCA], [https://pdbe.org/7mwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mwn RCSB], [https://www.ebi.ac.uk/pdbsum/7mwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mwn ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PYL2_ARATH PYL2_ARATH] Receptor for abscisic acid (ABA) required for ABA-mediated responses such as stomatal closure and germination inhibition. Inhibits the activity of group-A protein phosphatases type 2C (PP2Cs) when activated by ABA.<ref>PMID:19898420</ref> <ref>PMID:19893533</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A general method to generate biosensors for user-defined molecules could provide detection tools for a wide range of biological applications. Here, we describe an approach for the rapid engineering of biosensors using PYR1 (Pyrabactin Resistance 1), a plant abscisic acid (ABA) receptor with a malleable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which facilitates the construction of sense-response functions. We applied this platform to evolve 21 sensors with nanomolar to micromolar sensitivities for a range of small molecules, including structurally diverse natural and synthetic cannabinoids and several organophosphates. X-ray crystallography analysis revealed the mechanistic basis for new ligand recognition by an evolved cannabinoid receptor. We demonstrate that PYR1-derived receptors are readily ported to various ligand-responsive outputs, including enzyme-linked immunosorbent assay (ELISA)-like assays, luminescence by protein-fragment complementation and transcriptional circuits, all with picomolar to nanomolar sensitivity. PYR1 provides a scaffold for rapidly evolving new biosensors for diverse sense-response applications.
-Authors: Peterson, F.C., Beltran, J., Bedewitz, M., Steiner, P.J., Cutler, S.R., Whitehead, T.A.
+Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds.,Beltran J, Steiner PJ, Bedewitz M, Wei S, Peterson FC, Li Z, Hughes BE, Hartley Z, Robertson NR, Medina-Cucurella AV, Baumer ZT, Leonard AC, Park SY, Volkman BF, Nusinow DA, Zhong W, Wheeldon I, Cutler SR, Whitehead TA Nat Biotechnol. 2022 Jun 20. doi: 10.1038/s41587-022-01364-5. PMID:35726092<ref>PMID:35726092</ref>
-Description: An engineered PYL2-based WIN 55,212-2 synthetic cannabinoid sensor with a stabilized HAB1 variant
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Steiner, P.J]]
+<div class="pdbe-citations 7mwn" style="background-color:#fffaf0;"></div>
-[[Category: Cutler, S.R]]
-[[Category: Peterson, F.C]]
+==See Also==
-[[Category: Bedewitz, M]]
+*[[Abscisic acid receptor 3D structures|Abscisic acid receptor 3D structures]]
-[[Category: Whitehead, T.A]]
+== References ==
-[[Category: Beltran, J]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Arabidopsis thaliana]]
+[[Category: Large Structures]]
+[[Category: Bedewitz M]]
+[[Category: Beltran J]]
+[[Category: Cutler SR]]
+[[Category: Peterson FC]]
+[[Category: Steiner PJ]]
+[[Category: Whitehead TA]]

7mwn: Difference between revisions

Revision as of 10:17, 14 December 2022

An engineered PYL2-based WIN 55,212-2 synthetic cannabinoid sensor with a stabilized HAB1 variant

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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