Melcher Laboratory

Selected Publications

Yang S, Wu T, Xu TH, de Waal PW, He Y, Pu M, Chen Y, DeBruine ZJ, Zhang B, Zaidi SA, Popov P, Guo Y, Han GW, Lu Y, Suino-Powell K, Song S, Harikumar KG, Miller LJ, Katritch V, Xu HE, Shui W, Stevens RC, Melcher K, Zhao S, Xu F. 2018. Crystal structure of the Frizzled 4 receptor in a ligand-free state. Nature.

Yin W, Zhou XE, Yang D, de Waal PW, Want M, Dai A, Cai X, Haung CY, Liu P, Wang X, Yin Y, Liu B, Zhou Y, Wang J, Liu H, Caffrey M, Melcher K, Xu Y, Wang MW, Xu HE, Jiang Y. 2018. Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist. Cell Disc 4(12).

Kang Y*, Kuybeda O*, de Waal PW*, Mukherjee S, Van Eps N, Dutka P, Zhou XE, Bartesaghi A, Erramilli S, Morizumi T, Gu X, Yin Y, Liu P, Jiang Y, Meng X, Zhao G, Melcher K, Ernst OP, Kossiakoff AA, Subramaniam S, Xu HE. 2018. Cryo-EM structure of human rhodopsin bound to an inhibitory G protein. Nature.     Article

Zhou XE, He Y, de Waal PW, Gao X, Kang Y, Van Eps N, Yin Y, Pal K, Goswami D, White TA, Barty A, Latorraca NR, Chapman HN, Hubbell WL, Dror RO, Stevens RC, Cherezov V, Gurevich VV, Griffin PR, Ernst OP, Melcher K, Xu HE. 2017. Identification of phosphorylation codes for arrestin recruitment by G protein-coupled receptors. Cell 170(3):457–469.e13.    Article
*Cover of Cell

He Y, Gao X, Goswami D, Hou L, Pal K, Yin Y, Zhao G, Ernst OP, Griffin P, Melcher K, Xu HE. 2017. Molecular assembly of rhodopsin with G protein-coupled receptor kinases. Cell Res doi: 10.1038/cr.2017.72.     PubMed

Ma H, Duan J, Ke J, He Y, Gu X, Xu TH, Yu H, Wang Y, Brunzelle JS, Jiang Y, Rothbart SB, Xu HE, Li J, Melcher K. 2017. A D53 repression motif induces oligomerization of TOPLESS copressors and promotes assembly of a corepressor-nucleosome complex. Sci Adv.    Article

DeBruine ZJ, Ke J, Harikumar KG, Gu X, Borowsky P, Williams BO, Xu W, Miller LJ, Xu HE*, Melcher K*. 2017. Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization. Genes Dev.    Article
*Corresponding authors

Yin Y, de Waal P, He Y, Zhao LH, Yang D, Cai X, Jiang Y, Melcher K, Wang MW, Xu HE. 2017. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors. J Bio Chem.    Article
*Editors’ Pick:  top 2% of JBC papers

Feng Z, Ke J, Zhang L Chen R, Sugimoto K, Howe GA, Xu HE, Zhou M*, He SY*, Melcher K*. 2017. Structural insights into alternative splicing-mediated desensitization of jasmonate signaling. Proc Natl Acad Sci U S A 114(7):1720–1725.    Article
*Corresponding authors

Melcher K. 2016. When sperm meets egg. Nature 534:484–485.    Article

Zhao L-H, Zhou XE, Yi W, Wu Z, Liu Y, Kang Y, Hou L, de Waal PW, Li S, Jiang Y, Scaffidi A, Flematti GR, Smith SM, Lam VQ, Griffin PR, Wang Y, Li J, Melcher K*, Xu HE*. 2015. Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3. Cell Res 25:1219–1236.    Article
*Corresponding authors

Ke J, Ma H, Gu X, Thelen A, Brunzelle JS, Li J, Xu HE, Melcher K. 2015. Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors. Sci Adv 1(6):e1500107    Article

Zhang F, Yao J, Ke J, Zhang L, Lam VQ, Xin X-F, Zhou XE, Chen J, Brunzelle J, Griffin PR, Zhou M, Xu HE, Melcher K, He YS. 2015. Structural basis of JAZ-mediated repression of MYC transcription factors in jasmonate signaling. Nature 525(7568): 269–273    PubMed

Shen G, Ke J, Wang Z, Cheng Z, Gu X, Wei Y, Melcher K, Xu HE, Xu W. Structural basis of the Norrin-Frizzled 4 interaction. Cell Res 25:1078–1081     Article

Kang Y, Zhou XE Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MHE, Zhang C, Moeller A, West GM, Pascal B, Eps NV, Caro1 LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi XY, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad C, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N,  Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JCH, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE 2015. Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser. Nature     Article
*Featured in Nature News & Views

Zhi, X., Zhou, XE, He Y, Searose-Xu K, Zhang C-L, Tsai CC, Melcher K, Xu HE. 2015.  Structural basis for corepressor assembly by the orphan nuclear receptor TLX. Genes Dev 29(4):440-450.     PubMed

Sridharamurthy M, Kovach A, Zhao Y, Zhu JK, Xu HE, Swaminathan K, and Melcher K 2014. H2O2 inhibits ABA-signaling protein phosphatase HAB1. PLoS One 9(12):e113643.     PubMed

Li X*, Wang L*, Zhou XE*, Ke J, de Waal PW, Gu X, Tan MHE, Wang D, Wu D, Xu HE, Melcher K. 2014. Structural basis of AMPK regulation by adenine nucleotides and glycogen. Cell Res 25(1):50-66.     PubMed     
*Authors contributed equally to this work
**Highlighted in Editorial in Cell Research

He Y, Yi W, Powell K, Zhou XE, Tolbert DW, Tang X, Yang J, Yang H, Shi J, Hou L, Jiang H, Melcher K, Xu HE 2014. Structures and mechanism for the design of highly potent glucocorticoids.  Cell Res 24(6):713–726.    PubMed

Pal K, Melcher, K, Xu, HE 2013.  Structure modeling using genetically engineered crosslinking.  Cell 155(6):1207-1208.     PubMed

Jiang L, Liu X, Xiong GS, Liu HH, Chen F, Wang L, Meng XB, Liu GF, Yu Y, Yuan YD, Yi W, Zhao LH, Ma HL, He YZ, Wu ZS, Melcher K, Qian Q, Xu HE, Wang YH, Li JY. 2013. DWARF 53 acts as a repressor of strigolactone signalling in rice. Nature 504(7480):401-405.     PubMed

Ke J, Chen R-Z, Ban T, Zhou XE, Gu X, M. H. Tan MHE, Chen C, Kang Y, Brunzelle JS, Zhu J-K, Melcher K, Xu HE. 2013. Structural basis for RNA recognition by a dimeric PPR protein complex.  Nat Struct Mol Biol 20(12):1377-1382.     PubMed

Ke J, Harikumar KG, Jurecky C, Chen C, WangL, Parker N, Gu X, Cheng Z, Xu W, Williams BO, Melcher K, Miller LJ and Xu HE.  2013.  Structure and function of Norrin in assembly and activation of a Frizzled 4 – Lrp5/6 complex.  Genes Dev 27(21):2305-2319.     PubMed
*Genes & Development cover article

Chen C*, Ke J*, Zhou XE, Yi W, Brunzelle JS, Li J, Yong E-L, Xu HE, and Melcher K. 2013. Structural basis for molecular recognition of folic acid by folate receptors.  Nature 500(7463):486-489.     PubMed     Article  
*Authors contributed equally to this work
**Highlighted as ACS Chem Biol spotlight
***Highlighted as Chem Engin News’s “News of the Week”

Wang C*, Jiang Y*, Ma J*, Wu H, Wacker D, Katritch V, Han GW, Liu W, Huang XP, Vardy E, McCorvy JD, Gao X, Zhou XE, Melcher K, Zhang C, Bai F, Yang H, Yang L, Jiang H, Roth BL, Cherezov V, Stevens RC*, Xu HE*. 2013. Structural Basis for Molecular Recognition of Serotonin Receptors.  Science 340(6132):610-614.     PubMed     Article
*These authors contributed equally to this work
**Highlighted as editorials in Science, Nature and Chem Eng News.

Zhao LH*, Zhou XE*, Wu ZS*, Yi W, Xu Y, Li S, Xu TH, Liu Y, Chen RZ, Kovach A, Kang Y, Hou L, He Y, Xie C, Song W, Zhong D, Xu Y, Wang Y, Li J, Zhang C*, Melcher K, Xu HE. 2013. Crystal structures of two phytohormone signal-transducing α/β hydrolases: karrikin-signaling KAI2 and strigolactone-signaling DWARF 14. Cell Res 23(3):436-439.     PubMed
*Authors contributed equally to this work

Soon FF, Suino-Powell KM, Li J, Yong E-L, Xu HE, and Melcher K. 2012. Abscisic acid signaling: Thermal stability shift assays as tool to analyze hormone perception and signal transduction. PLoS ONE 7(10):e47857.     PubMed

Zhou XE*, Soon FF*, Ng LM*, Kovach A, Suino-Powell KM, Li J, Yong EL, Zhu JK, Xu HE, Melcher K. 2012.
Catalytic mechanism and kinase interactions of ABA-signaling PP2C phosphatases. Plant Signal Behav 7(5):581-588.     PubMed
*Authors contributed equally to this work

Soon FF*, Ng L-M*, Zhou XE*, West GM, Kovach A, Tan MHE, Suino-Powell KM, He Y, Xu Y, Chalmers M, Brunzelle J, Zhang H, Yang H, Jiang H,  Li J, Yong E-L, Zhu J-K, Griffin PR, Cutler S, Melcher K, and Xu HE. 2012. Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases. Science 335(6064):85-88.     PubMed     Article
*Authors contributed equally to this work
**Highlighted in an editorial in Science, Science Signaling Editor’s Choice and as a research highlight in Nature Chem Biol

Ng LM, Soon FF, Zhou XE, West GM, Kovach A, Suino-Powell KM, Chalmers MJ, Li J, Yong EL, Zhu JK, Griffin PR, Melcher K, Xu HE. 2011. 
Structural basis for basal activity and autoactivation of abscisic acid (ABA) signaling SnRK2 kinases. Proc Natl Acad Sci U S A 108(52):21259-21264     PubMed
*Research Highlight in Nature Chem Biol

Melcher, K, Zhou XE, and Xu, HE. 2010. Thirsty plants and beyond: Structural mechanisms of abscisic acid perception and signaling. Curr Opin Struct Biol 20(6):722-729     PubMed

Melcher K, Xu Y, Ng L-M, Zhou XE, Soon F-F, Chinnusamy V., Suino-Powell KM, Kovach A, Tham FS, Cutler SR, Li J., Yong E-L, Zhu J-K, and Xu HE. 2010. Identification and mechanism of ABA receptor antagonism.  Nat Struct Mol Biol 17(9)1102–1108     PubMed
*Featured as Research Advance in PSI Nature Structural Biology Knowledgebase and as an editorial in Nature Struct Mol Biol 

Zhong P, and Melcher K. 2010. Identification and characterization of the activation domain of Ifh1, an activator of model TATA-less genes.  Biochem Biophys Res Comm 392(1):77-82.     PubMed

Melcher K*, Ng L-M*, Zhou XE*, Soon FF*, Xu Y, Suino-Powell KM, Park SY, Weiner JJ, Fujii H, Chinnusamy V, Kovach A, Li J, Wang Y, Li Y, Peterson FC, Jensen DR, Yong E-L, Volkman BF, Cutler SR, Zhu J-K, and Xu HE. 2009. A gate–latch–lock mechanism for hormone signalling by abscisic acid receptors. Nature 462(7273):602-608.     PubMed     Article
*Contributed equally to this work
**Nature Cover Article and highlighted as editorial in Nature
***Featured as one of top 10 Breakthroughs of 2009 by Science Magazine, one of Top 10 Signaling Breakthroughs by Science Signaling and Research Highlights by Nature Cell Biology and Science Signaling

Melcher K and Chen H-T. 2007 Identification and analysis of multiprotein complexes through chemical crosslinking. Curr Protoc Cell Biol 17(17.10)     PubMed

Melcher K. (2005) Mutational hypersensitivity of a gene regulatory protein: S. cerevisiae Gal80p. Genetics 171(2):469-476.     PubMed

Melcher K. (2004) New chemical crosslinking methods for the identification of transient protein-protein interactions with multiprotein complexes. Curr Protein Pept Sci 5(4):287-296.     PubMed

Klein J, Nolden M, Sanders S, Kirchner J, Weil PA and Melcher K. (2003). Use of a genetically introduced cross-linker to identify interaction sites of acidic activators within native transcription factor IID and SAGA. J. Biol. Chem. 278(9):6779-6786     PubMed

Melcher K. and Xu HE. 2001 Gal80-Gal80 interaction on adjacent Gal4p binding sites is required for complete GAL gene repression. EMBO J 20(4)841-851.     PubMed

Melcher K. (2000). The strength of acidic activation domains correlates with their affinity for both transcriptional and non-transcriptional proteins. J Mol Biol 301(5):1097-1112.     PubMed

Melcher K, Sharma B, Ding WV, Nolden M. (2000). Zero background yeast reporter plasmids. Gene 247(1-2):53-61.     PubMed

Melcher K, (2000). A modular set of prokaryotic and eukaryotic expression plasmids. Anal. Biochem. 277(1): 109-120.     PubMed

Swaffield JC, Melcher K, and Johnston, SA (1995). A highly conserved ATPase protein as a mediator between acidic activation domains and the TATA-binding protein. Nature 374(6517):88-91. [see correction Nature 379, 658]     PubMed

Melcher K, Johnston SA, 1995. GAL4 interacts with TATA-binding protein and coactivators. Mol. Cell. Biol 15(5)2839-2848.     PubMed