Editors' ChoiceReceptor Activation

A lock that cuts its own key

Sci. Signal.  30 Aug 2016:
Vol. 9, Issue 443, pp. ec196
DOI: 10.1126/scisignal.aai8870

As a general rule, ligands bind to their cognate receptor noncovalently and induce a conformational change in the receptor that activates the receptor or enables it to interact with binding partners. Yao et al. and de Saint Germain et al. report that the α/β hydrolase DWARF14 (D14) is a strigolactone receptor, and this unusual receptor not only hydrolyzes its ligand but also forms a covalent attachment to the modified ligand. Strigolactones are carotenoid-derived plant hormones that regulate many developmental processes and trigger the germination of parasitic plants. One of the molecular processes triggered by strigolactones is the proteasomal degradation of D14. Orthologs of D14 from Arabidopsis thaliana (thale cress, Yao et al.), Pisum sativum (pea, de Saint Germain et al.), and Oryza sativa (rice, de Saint Germain et al.) hydrolyzed biologically active strigolactones and became covalently bound to one of the hydrolysis products. Through structural analysis of Arabidopsis D14 (AtD14) in complex with two of the proteins that promote its degradation, Yao et al. found that becoming covalently attached to the strigolactone hydrolysis product elicited a conformational change in AtD14 that enabled AtD14 to interact with its binding partners. Arabidopsis d14-5 mutants display phenotypes characteristic of impaired strigolactone signaling and have a single amino acid substitution in AtD14 that was predicted to affect a structural feature that is involved in the strigolactone-induced conformational change. This mutation did not affect the enzymatic activity of AtD14 but prevented AtD14 from interacting with one of its binding partners. de Saint Germain et al. found that a strigolactone analog that was not biologically active was hydrolyzed by RMS3, the pea ortholog of D14, but the product failed to stably associate with the receptor, supporting the idea that covalent attachment of the hydrolysis product is important for strigolactone signaling. Results from kinetic analysis of the pea ortholog of D14 were consistent with each RMS3 molecule performing only a single round of catalysis. These findings present a new paradigm in ligand-receptor interaction and raise many additional questions, including how different strigolactones can elicit distinct responses and whether the receptors function as single-turnover enzyme in vivo (see Snowden and Janssen).

R. Yao, Z. Ming, L. Yan, S. Li, F. Wang, S. Ma, C. Yu, M. Yang, L. Chen, L. Chen, Y. Li, C. Yan, D. Miao, Z. Sun, J. Yan, Y. Sun, L. Wang, J. Chu, S. Fan, W. He, H. Deng, F. Nan, J. Li, Z. Rao, Z. Lou, D. Xie, DWARF14 is a non-canonical hormone receptor for strigolactone. Nature 536, 469–473 (2016). [PubMed]

A. de Saint Germain, G. Clavé, M.-A. Badet-Denisot, J. P. Pillot, D. Cornu, J.-P. Le Caer, M. Burger, F. Pelissier, P. Retailleau, C. Turnbull, S. Bonhomme, J. Chory, C. Rameau, F.-D. Boyer, An histidine covalent receptor and butenolide complex mediates strigolactone perception. Nat. Chem. Biol. 10.1038/nchembio.2147 (2016). [PubMed]

K. C. Snowden, B. J. Janssen, Signal locked in. Nature 536, 402–404 (2016). [PubMed]

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