7MWN
An engineered PYL2-based WIN 55,212-2 synthetic cannabinoid sensor with a stabilized HAB1 variant
Summary for 7MWN
| Entry DOI | 10.2210/pdb7mwn/pdb |
| Descriptor | Abscisic acid receptor PYL2, HAB1-T+, {(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, ... (9 entities in total) |
| Functional Keywords | pyr/pyl/rcar, pyl2, hormone receptor, plant protein, biosensor, cannabinoid |
| Biological source | Arabidopsis thaliana (Mouse-ear cress) More |
| Total number of polymer chains | 2 |
| Total formula weight | 58893.58 |
| Authors | Peterson, F.C.,Beltran, J.,Bedewitz, M.,Steiner, P.J.,Cutler, S.R.,Whitehead, T.A. (deposition date: 2021-05-17, release date: 2022-06-01, Last modification date: 2023-10-25) |
| Primary citation | Beltran, J.,Steiner, P.J.,Bedewitz, M.,Wei, S.,Peterson, F.C.,Li, Z.,Hughes, B.E.,Hartley, Z.,Robertson, N.R.,Medina-Cucurella, A.V.,Baumer, Z.T.,Leonard, A.C.,Park, S.Y.,Volkman, B.F.,Nusinow, D.A.,Zhong, W.,Wheeldon, I.,Cutler, S.R.,Whitehead, T.A. Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds. Nat.Biotechnol., 40:1855-1861, 2022 Cited by PubMed Abstract: 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. PubMed: 35726092DOI: 10.1038/s41587-022-01364-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.902 Å) |
Structure validation
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