@article{paczkowski_mccready_cong_li_jeffrey_smith_henke_hughson_bassler_2019, title={An Autoinducer Analogue Reveals an Alternative Mode of Ligand Binding for the LasR Quorum-Sensing Receptor}, volume={14}, ISSN={["1554-8937"]}, DOI={10.1021/acschembio.8b00971}, abstractNote={Bacteria use a cell-cell communication process called quorum sensing to coordinate collective behaviors. Quorum sensing relies on production and group-wide detection of extracellular signal molecules called autoinducers. Here, we probe the activity of the Pseudomonas aeruginosa LasR quorum-sensing receptor using synthetic agonists based on the structure of the native homoserine lactone autoinducer. The synthetic compounds range from low to high potency, and agonist activity tracks with the ability of the agonist to stabilize the LasR protein. Structural analyses of the LasR ligand binding domain complexed with representative synthetic agonists reveal two modes of ligand binding, one mimicking the canonical autoinducer binding arrangement, and the other with the lactone head group rotated approximately 150°. Iterative mutagenesis combined with chemical synthesis reveals the amino acid residues and the chemical moieties, respectively, that are key to enabling each mode of binding. Simultaneous alteration of LasR residues Thr75, Tyr93, and Ala127 converts low-potency compounds into high-potency compounds and converts ligands that are nearly inactive into low-potency compounds. These results show that the LasR binding pocket displays significant flexibility in accommodating different ligands. The ability of LasR to bind ligands in different conformations, and in so doing, alter their potency as agonists, could explain the difficulties that have been encountered in the development of competitive LasR inhibitors.}, number={3}, journal={ACS CHEMICAL BIOLOGY}, author={Paczkowski, Jon E. and McCready, Amelia R. and Cong, Jian-Ping and Li, Zhijie and Jeffrey, Philip D. and Smith, Chari D. and Henke, Brad R. and Hughson, Frederick M. and Bassler, Bonnie L.}, year={2019}, month={Mar}, pages={378–389} }
 @article{li_chakraborty_xu_2017, title={Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions}, volume={12}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0175317}, abstractNote={Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65 Ǻ and 2.75 Ǻ respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).}, number={4}, journal={PLOS ONE}, author={Li, Zhijie and Chakraborty, Sayan and Xu, Guozhou}, year={2017}, month={Apr} }
 @article{boyaci_shah_hurley_kokona_li_ventocilla_jeffrey_semmelhack_fairman_bassler_et al._2016, title={Structure, regulation, and inhibition of the quorum-sensing signal integrator LuxO}, volume={14}, number={5}, journal={PLoS Biology}, author={Boyaci, H. and Shah, T. and Hurley, A. and Kokona, B. and Li, Z. J. and Ventocilla, C. and Jeffrey, P. D. and Semmelhack, M. F. and Fairman, R. and Bassler, B. L. and et al.}, year={2016} }
 @article{li_chakraborty_xu_2016, title={X-ray crystallographic studies of the extracellular domain of the first plant ATP receptor, DORN1, and the orthologous protein from Camelina sativa}, volume={72}, ISSN={["2053-230X"]}, DOI={10.1107/s2053230x16014278}, abstractNote={Does not respond to nucleotides 1 (DORN1) has recently been identified as the first membrane-integral plant ATP receptor, which is required for ATP-induced calcium response, mitogen-activated protein kinase activation and defense responses inArabidopsis thaliana. In order to understand DORN1-mediated ATP sensing and signal transduction, crystallization and preliminary X-ray studies were conducted on the extracellular domain of DORN1 (atDORN1-ECD) and that of an orthologous protein,Camelina sativalectin receptor kinase I.9 (csLecRK-I.9-ECD or csI.9-ECD). A variety of deglycosylation strategies were employed to optimize the glycosylated recombinant atDORN1-ECD for crystallization. In addition, the glycosylated csI.9-ECD protein was crystallized at 291 K. X-ray diffraction data were collected at 4.6 Å resolution from a single crystal. The crystal belonged to space groupC222 orC2221, with unit-cell parametersa= 94.7,b= 191.5,c= 302.8 Å. These preliminary studies have laid the foundation for structural determination of the DORN1 and I.9 receptor proteins, which will lead to a better understanding of the perception and function of extracellular ATP in plants.}, journal={ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS}, author={Li, Zhijie and Chakraborty, Sayan and Xu, Guozhou}, year={2016}, month={Oct}, pages={782–787} }