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研究领域

Structural studies of environmental sensor proteins, aiming to gain insight into natural regulation and understand how to apply these principles for artificial control

Our lab studies environmentally-switched protein/protein interaction domains about their natural regulation and understand how to artificially control them in vitro and in living cells. This is exemplified by our work on photosensors, parts of the hypoxia response, and others.

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74. Guo, Y., Scheuermann, T.H., Partch, C.L., Tomchick, D.R. and Gardner, K.H. (2015) Coiled-coil coactivators play a structural role mediating interactions in hypoxia inducible factor heterodimerization. J. Biol. Chem., 290: 7707-7721. ( Abstract and full text ) 73. Ocasio, V., Corrêa, F. and Gardner, K.H. (2015) Ligand-induced folding of a two component signaling receiver domain. Biochemistry, 54: 1353-1363. ( Abstract and full text ) 72. Rivera-Cancel, G., Ko, W.-H., Tomchick, D.R., Corrêa, F. and Gardner, K.H. (2014) Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation. Proc. Natl. Acad. Sci., 111: 17839-17844. ( Abstract and full text | Recommended at F1000 ) 71. Motta-Mena, L.B., Reade, A., Mallory, M.J., Glantz, S., Weiner, O.D., Lynch, K.W. and Gardner, K.H. (2014) An optogenetic gene expression system with rapid activation and deactivation kinetics. Nat. Chem. Biol., 10: 196-202. ( Abstract and full text ) 70. Salomon, D., Guo, Y., Kinch, L.N., Grishin, N.V., Gardner, K.H. and Orth, K. (2013) Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides. Nat. Comm., 4: 2973. ( Abstract and full text ) 69. Zoltowski, B.D., Motta-Mena, L.B. and Gardner K.H. (2013) Blue-light induced dimerization of a bacterial LOV-HTH DNA-binding protein. Biochemistry, 52: 6653-6661. ( Abstract and full text ) 68. Corrêa, F., Ko, W.-H., Ocasio, V., Bogomolni, R.A. and Gardner, K.H. (2013) Blue light regulated two-component systems: Enzymatic and functional analyses of Light-Oxygen-Voltage(LOV)-histidine kinases and downstream response regulators. Biochemistry, 52: 4656-4666. ( Abstract and full text ) 67. Rogers, J.L.*, Bayeh, L.*, Scheuermann, T.H.*, Longgood, J., Key, J., Naidoo, J., Melito, L., Shokri, C., Frantz, D.E., Bruick, R.K., Gardner, K.H., MacMillan, J.B. and Tambar, U.K. (2013) Development of inhibtors of the PAS-B domain of the HIF-2α transcription factor. J. Med. Chem., 56: 1739-1747. ( Abstract and full text ) (*: equal contributions) 66. Scheuermann, T.H., Li, Q., Ma, H.-W., Key, J., Zhang, L., Chen, R., Garcia, J.A., Naidoo, J., Longgood, J., Frantz, D.E., Tambar, U.K., Gardner, K.H. and Bruick, R.K. (2013) Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat. Chem. Biol., 9: 271-276. ( Abstract and full text ) 65. Freddolino, P.L., Gardner, K.H. and Schulten, K. (2013) Signaling mechanisms of LOV domains: New insights from molecular dynamics studies. Photochem. Photobiol. Sci., 12: 1158-1170. ( Abstract and full text ) 64. Moon, T.M., Corrêa, F., Kinch, L.N., Piala, A.T., Gardner, K.H. and Goldsmith, E.J. (2013) Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2 domain. J. Mol. Biol., 425: 1245-1252. ( Abstract and full text ) 63. Guo, Y., Partch, C.L., Key, J., Card, P.B., Pashkov, V., Patel, A., Bruick, R.K., Wurdak, H. and Gardner, K.H. (2013) Regulating the ARNT/TACC3 axis: Multiple approaches to manipulating protein/protein interactions with small molecules. ACS Chemical Biology, 8: 626-635. ( Abstract and full text ) 62. Rivera-Cancel, G.*, Motta-Mena, L.B.* and Gardner, K.H. (2012) Identification of natural and artificial DNA substrates for light-activated LOV-HTH transcription factor EL222. Biochemistry, 51: 10024-10034. ( Abstract and full text ) (*: equal contributions) 61. Chollangi, S., Thompson, J.W., Ruiz, J.C., Gardner, K.H. and Bruick, R.K. (2012) The hemerythrin-like domain within F-box and leucine-rich repeat protein 5 communicates cellular iron and oxygen availability by distinct mechanisms. J. Biol. Chem., 287: 23710-23717. ( Abstract and full text ) 60. Zoltowski, B.D., Nash, A.I. and Gardner, K.H. (2011) Variations in protein/flavin hydrogen bonding in a LOV domain produce non-Arrhenius kinetics of adduct decay. Biochemistry (Accelerated Publication), 50: 8771-8779. ( Abstract and full text ) 59. Yuan, H., Dragnea, V., Wu, Q., Gardner, K.H. and Bauer, C.E. (2011) Mutational and structural studies of the PixD BLUF outputsignal that affects light-regulated interactions with PixE. Biochemistry, 50: 6365-6375. ( Abstract and full text ) 58. Nash, A.I.*, McNulty, R.*, Shillito, M.E., Swartz, T.E., Bogomolni, R.A., Luecke, H. and Gardner, K.H. (2011) Structural basis of photosensitivity in a bacterial light-oxygen-voltage/helix-turn-helix (LOV-HTH) DNA-binding protein. Proc. Natl. Acad. Sci. USA, 108: 9449-9454. ( Abstract and full text ) (*: equal contributions) 57. Partch, C.L. and Gardner, K.H. (2011) Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B. Proc. Natl. Acad. Sci. USA, 108: 7739-7744. ( Abstract and full text ) 56. Song, S.-H., Freddolino, P.L., Nash, A.I., Carroll, E.C., Schulten, K., Gardner, K.H. and Larsen, D.S. (2011) Modulating LOV domain photodynamics with a residue alteration outside the chromophore binding site. Biochemistry (Accelerated Publication), 50: 2411-2423. ( Abstract and full text ) 55. Zoltowski, B.D. and Gardner, K.H. (2011) Tripping the Light Fantastic: Blue-light photoreceptors as examples of environmentally modulated protein-protein interactions. Biochemistry, 50: 4-16. ( Abstract and full text )

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