616.234.5000

Publications

Melcher Laboratory

Selected Publications

Yan Y, Zhou EX, Novick SJ, Shaw SJ, Li Y, Brunzelle JS, Hitoshi Y, Griffin PR, Xu HE, Melcher K. 2019. Structures of AMP-activated protein kinase bound to novel pharmacological activators in phosphorylated, non-phosphorylated and nucleotide-free states. J Biol Chem 294(3):953–967.

Gu X, Bridges MD, Yan Y, de Waal PW, Zhou EX, Suino-Powell KM, Xu HE, Hubbell WL, Melcher K. 2018. Conformational heterogeneity of the allosteric drug and metabolite (ADaM) site in AMP-activated protein kinase (AMPK). J Biol Chem 293(44):16994–17007.

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 560:666–670.

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 proteinNature 558:553–558. 
*Contributed equally

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.
*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 27(6):728–747.

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 3:e1601217.

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 31:916–926.   
*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.    
*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.    
*Corresponding authors

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

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.    
*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.    

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.    

Shen G, Ke J, Wang Z, Cheng Z, Gu X, Wei Y, Melcher K, Xu HE, Xu W. 2015. Structural basis of the Norrin-Frizzled 4 interaction. Cell Res 25:1078–1081.  

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 laserNature 523:561–567.   
*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.     

Sridharamurthy M, Kovach A, Zhao Y, Zhu JK, Xu HE, Swaminathan K, Melcher K 2014. H2O2 inhibits ABA-signaling protein phosphatase HAB1PLoS One 9(12):e113643.  

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 glycogenCell Res 25(1):50-66.  
*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.    

Pal K, Melcher, K, Xu, HE 2013. Structure modeling using genetically engineered crosslinkingCell 155(6):1207–1208.     

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 riceNature 504(7480):401–405.       

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 complexNat Struct Mol Biol 20(12):1377–1382.     

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

Chen C*, Ke J*, Zhou XE, Yi W, Brunzelle JS, Li J, Yong E-L, Xu HE, Melcher K. 2013. Structural basis for molecular recognition of folic acid by folate receptorsNature 500(7463):486–489.     
*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 receptorsScience 340(6132):610–614.     
*These authors contributed equally to this work
**Highlighted as editorials in ScienceNature 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 14Cell Res 23(3):436–439.     
*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, Xu HE. 2012. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatasesScience 335(6064):85–88.     
*Authors contributed equally to this work
**Highlighted in an editorial in ScienceScience 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 kinasesProc Natl Acad Sci U S A 108(52):21259–21264.     
*Research Highlight in Nature Chem Biol

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

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 antagonismNat Struct Mol Biol 17(9)1102–1108.     
*Featured as research advance in PSI Nature Structural Biology Knowledgebase and as an editorial in Nature Struct Mol Biol 

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 receptorsNature 462(7273):602–608.     
*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 Magazineone of Top 10 Signaling Breakthroughs by Science Signaling and Research Highlights by Nature Cell Biology and Science Signaling