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A complex structure of arrestin-2 bound to a G protein-coupled receptor.

Yin W, Li Z, Jin M, Yin YL, de Waal PW, Pal K, Yin Y, Gao X, He Y, Gao J, Wang X, Zhang Y, Zhou H, Melcher K, Jiang Y, Cong Y, Edward Zhou X, Yu X, Eric Xu H.

Cell Res. 2019 Dec;29(12):971-983. doi: 10.1038/s41422-019-0256-2. Epub 2019 Nov 27.


Crystallization of a Complex Between MYC and Jas Motif.

Zhang F, He SY, Melcher K.

Methods Mol Biol. 2020;2085:133-144. doi: 10.1007/978-1-0716-0142-6_10.


Development of "Plug and Play" Fiducial Marks for Structural Studies of GPCR Signaling Complexes by Single-Particle Cryo-EM.

Dutka P, Mukherjee S, Gao X, Kang Y, de Waal PW, Wang L, Zhuang Y, Melcher K, Zhang C, Xu HE, Kossiakoff AA.

Structure. 2019 Dec 3;27(12):1862-1874.e7. doi: 10.1016/j.str.2019.10.004. Epub 2019 Oct 25.


Structure and dynamics of the active human parathyroid hormone receptor-1.

Zhao LH, Ma S, Sutkeviciute I, Shen DD, Zhou XE, de Waal PW, Li CY, Kang Y, Clark LJ, Jean-Alphonse FG, White AD, Yang D, Dai A, Cai X, Chen J, Li C, Jiang Y, Watanabe T, Gardella TJ, Melcher K, Wang MW, Vilardaga JP, Xu HE, Zhang Y.

Science. 2019 Apr 12;364(6436):148-153. doi: 10.1126/science.aav7942.


Development of highly potent glucocorticoids for steroid-resistant severe asthma.

He Y, Shi J, Nguyen QT, You E, Liu H, Ren X, Wu Z, Li J, Qiu W, Khoo SK, Yang T, Yi W, Sun F, Xi Z, Huang X, Melcher K, Min B, Xu HE.

Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6932-6937. doi: 10.1073/pnas.1816734116. Epub 2019 Mar 20.


Structures of AMP-activated protein kinase bound to novel pharmacological activators in phosphorylated, non-phosphorylated, and nucleotide-free states.

Yan Y, Zhou XE, Novick SJ, Shaw SJ, Li Y, Brunzelle JS, Hitoshi Y, Griffin PR, Xu HE, Melcher K.

J Biol Chem. 2019 Jan 18;294(3):953-967. doi: 10.1074/jbc.RA118.004883. Epub 2018 Nov 26.


Structure and Physiological Regulation of AMPK.

Yan Y, Zhou XE, Xu HE, Melcher K.

Int J Mol Sci. 2018 Nov 9;19(11). pii: E3534. doi: 10.3390/ijms19113534. Review.


Structural biology of G protein-coupled receptor signaling complexes.

Edward Zhou X, Melcher K, Eric Xu H.

Protein Sci. 2019 Mar;28(3):487-501. doi: 10.1002/pro.3526. Epub 2018 Dec 13. Review.


Conformational heterogeneity of the allosteric drug and metabolite (ADaM) site in AMP-activated protein kinase (AMPK).

Gu X, Bridges MD, Yan Y, de Waal PW, Zhou XE, Suino-Powell KM, Xu HE, Hubbell WL, Melcher K.

J Biol Chem. 2018 Nov 2;293(44):16994-17007. doi: 10.1074/jbc.RA118.004101. Epub 2018 Sep 11.


Crystal structure of the Frizzled 4 receptor in a ligand-free state.

Yang S, Wu Y, 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, Dong S, Harikumar KG, Miller LJ, Katritch V, Xu HE, Shui W, Stevens RC, Melcher K, Zhao S, Xu F.

Nature. 2018 Aug;560(7720):666-670. doi: 10.1038/s41586-018-0447-x. Epub 2018 Aug 22.


Publisher Correction: Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.

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.

Nature. 2018 Sep;561(7724):E44. doi: 10.1038/s41586-018-0302-0.


Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.

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.

Nature. 2018 Jun;558(7711):553-558. doi: 10.1038/s41586-018-0215-y. Epub 2018 Jun 13. Erratum in: Nature. 2018 Jun 21;:.


Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist.

Yin W, Zhou XE, Yang D, de Waal PW, Wang M, Dai A, Cai X, Huang 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.

Cell Discov. 2018 Mar 13;4:12. doi: 10.1038/s41421-018-0009-2. eCollection 2018.


A Highly Sensitive Non-Radioactive Activity Assay for AMP-Activated Protein Kinase (AMPK).

Yan Y, Gu X, Xu HE, Melcher K.

Methods Protoc. 2018 Mar;1(1). pii: 3. doi: 10.3390/mps1010003. Epub 2017 Oct 13.


Bioluminescence Resonance Energy Transfer (BRET) Assay for Determination of Molecular Interactions in Living Cells.

Harikumar KG, Yan Y, Xu TH, Melcher K, Xu HE, Miller LJ.

Bio Protoc. 2017 Nov 20;7(22). pii: e2904. doi: 10.21769/BioProtoc.2904.


Streptavidin Bead Pulldown Assay to Determine Protein Homooligomerization.

Xu TH, Yan Y, Harikumar KG, Miller LJ, Melcher K, Xu HE.

Bio Protoc. 2017 Nov 20;7(22). pii: e2901. doi: 10.21769/BioProtoc.2901.


Detection of Membrane Protein Interactions by Cell-based Tango Assays.

Yan Y, Xu TH, Harikumar KG, Miller LJ, Melcher K, Xu HE.

Bio Protoc. 2017 Nov 20;7(22). pii: e2903. doi: 10.21769/BioProtoc.2903.


γ-Secretase Epsilon-cleavage Assay.

Xu TH, Yan Y, Harikumar KG, Miller LJ, Melcher K, Xu HE.

Bio Protoc. 2017 Nov 20;7(22). pii: e2900. doi: 10.21769/BioProtoc.2900.


Assembly and architecture of the Wnt/β-catenin signalosome at the membrane.

DeBruine ZJ, Xu HE, Melcher K.

Br J Pharmacol. 2017 Dec;174(24):4564-4574. doi: 10.1111/bph.14048. Epub 2017 Oct 18. Review.


Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites.

Yan Y, Xu TH, Harikumar KG, Miller LJ, Melcher K, Xu HE.

J Biol Chem. 2017 Sep 22;292(38):15826-15837. doi: 10.1074/jbc.M117.789669. Epub 2017 Aug 8.


Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors.

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.

Cell. 2017 Jul 27;170(3):457-469.e13. doi: 10.1016/j.cell.2017.07.002.


Amyloid beta: structure, biology and structure-based therapeutic development.

Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE.

Acta Pharmacol Sin. 2017 Sep;38(9):1205-1235. doi: 10.1038/aps.2017.28. Epub 2017 Jul 17. Review.


A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex.

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.

Sci Adv. 2017 Jun 2;3(6):e1601217. doi: 10.1126/sciadv.1601217. eCollection 2017 Jun.


Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing.

Gu X, Yan Y, Novick SJ, Kovach A, Goswami D, Ke J, Tan MHE, Wang L, Li X, de Waal PW, Webb MR, Griffin PR, Xu HE, Melcher K.

J Biol Chem. 2017 Jul 28;292(30):12653-12666. doi: 10.1074/jbc.M117.793018. Epub 2017 Jun 14.


Understanding the GPCR biased signaling through G protein and arrestin complex structures.

Zhou XE, Melcher K, Xu HE.

Curr Opin Struct Biol. 2017 Aug;45:150-159. doi: 10.1016/ Epub 2017 May 27. Review.


Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization.

DeBruine ZJ, Ke J, Harikumar KG, Gu X, Borowsky P, Williams BO, Xu W, Miller LJ, Xu HE, Melcher K.

Genes Dev. 2017 May 1;31(9):916-926. doi: 10.1101/gad.298331.117. Epub 2017 May 25.


Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases.

Pal K, Bandyopadhyay A, Zhou XE, Xu Q, Marciano DP, Brunzelle JS, Yerrum S, Griffin PR, Vande Woude G, Melcher K, Xu HE.

Structure. 2017 Jun 6;25(6):867-877.e3. doi: 10.1016/j.str.2017.04.015. Epub 2017 May 18.


Molecular assembly of rhodopsin with G protein-coupled receptor kinases.

He Y, Gao X, Goswami D, Hou L, Pal K, Yin Y, Zhao G, Ernst OP, Griffin P, Melcher K, Xu HE.

Cell Res. 2017 Jun;27(6):728-747. doi: 10.1038/cr.2017.72. Epub 2017 May 19.


Defining the minimum substrate and charge recognition model of gamma-secretase.

Yan Y, Xu TH, Melcher K, Xu HE.

Acta Pharmacol Sin. 2017 Oct;38(10):1412-1424. doi: 10.1038/aps.2017.35. Epub 2017 Apr 17.


Structure of the PRC2 complex and application to drug discovery.

Shi Y, Wang XX, Zhuang YW, Jiang Y, Melcher K, Xu HE.

Acta Pharmacol Sin. 2017 Jul;38(7):963-976. doi: 10.1038/aps.2017.7. Epub 2017 Apr 17. Review.


Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors.

Yin Y, de Waal PW, He Y, Zhao LH, Yang D, Cai X, Jiang Y, Melcher K, Wang MW, Xu HE.

J Biol Chem. 2017 Jun 16;292(24):9865-9881. doi: 10.1074/jbc.M117.782987. Epub 2017 Mar 29.


Structural insights into alternative splicing-mediated desensitization of jasmonate signaling.

Zhang F, Ke J, Zhang L, Chen R, Sugimoto K, Howe GA, Xu HE, Zhou M, He SY, Melcher K.

Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1720-1725. doi: 10.1073/pnas.1616938114. Epub 2017 Jan 30.


Identification of a novel selective PPARγ ligand with a unique binding mode and improved therapeutic profile in vitro.

Yi W, Shi J, Zhao G, Zhou XE, Suino-Powell K, Melcher K, Xu HE.

Sci Rep. 2017 Jan 27;7:41487. doi: 10.1038/srep41487.


An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain.

Yin Y, Zhou XE, Hou L, Zhao LH, Liu B, Wang G, Jiang Y, Melcher K, Xu HE.

Cell Discov. 2016 Nov 22;2:16042. eCollection 2016.


Alzheimer's disease-associated mutations increase amyloid precursor protein resistance to γ-secretase cleavage and the Aβ42/Aβ40 ratio.

Xu TH, Yan Y, Kang Y, Jiang Y, Melcher K, Xu HE.

Cell Discov. 2016 Aug 23;2:16026. doi: 10.1038/celldisc.2016.26. eCollection 2016.


The structural basis of the dominant negative phenotype of the Gαi1β1γ2 G203A/A326S heterotrimer.

Liu P, Jia MZ, Zhou XE, De Waal PW, Dickson BM, Liu B, Hou L, Yin YT, Kang YY, Shi Y, Melcher K, Xu HE, Jiang Y.

Acta Pharmacol Sin. 2016 Sep;37(9):1259-72. doi: 10.1038/aps.2016.69. Epub 2016 Aug 8.


Erratum: Discovery of a highly potent glucocorticoid for asthma treatment.

He Y, Shi J, Yi W, Ren X, Gao X, Li J, Wu N, Weaver K, Xie Q, Khoo SK, Yang T, Huang X, Melcher K, Xu HE.

Cell Discov. 2016 Jan 26;2:15051. doi: 10.1038/celldisc.2015.51. eCollection 2016.


Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.

Golani LK, Wallace-Povirk A, Deis SM, Wong J, Ke J, Gu X, Raghavan S, Wilson MR, Li X, Polin L, de Waal PW, White K, Kushner J, O'Connor C, Hou Z, Xu HE, Melcher K, Dann CE 3rd, Matherly LH, Gangjee A.

J Med Chem. 2016 Sep 8;59(17):7856-76. doi: 10.1021/acs.jmedchem.6b00594. Epub 2016 Aug 26.


Structural biology: When sperm meets egg.

Melcher K.

Nature. 2016 Jun 23;534(7608):484-5. doi: 10.1038/nature18448. Epub 2016 Jun 15. No abstract available.


Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.

Zhao LH, Yin Y, Yang D, Liu B, Hou L, Wang X, Pal K, Jiang Y, Feng Y, Cai X, Dai A, Liu M, Wang MW, Melcher K, Xu HE.

J Biol Chem. 2016 Jul 15;291(29):15119-30. doi: 10.1074/jbc.M116.726620. Epub 2016 May 13.


Generation and characterization of a human nanobody against VEGFR-2.

Ma L, Gu K, Zhang CH, Chen XT, Jiang Y, Melcher K, Zhang J, Wang M, Xu HE.

Acta Pharmacol Sin. 2016 Jun;37(6):857-64. doi: 10.1038/aps.2016.2. Epub 2016 Apr 25.


X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex.

Zhou XE, Gao X, Barty A, Kang Y, He Y, Liu W, Ishchenko A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Suino-Powell KM, Boutet S, Williams GJ, Wang M, Li D, Caffrey M, Chapman HN, Spence JC, Fromme P, Weierstall U, Stevens RC, Cherezov V, Melcher K, Xu HE.

Sci Data. 2016 Apr 12;3:160021. doi: 10.1038/sdata.2016.21.


Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors.

Ke J, Ma H, Gu X, Thelen A, Brunzelle JS, Li J, Xu HE, Melcher K.

Sci Adv. 2015 Jul 24;1(6):e1500107. doi: 10.1126/sciadv.1500107. eCollection 2015 Jul.


Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3.

Zhao LH, 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.

Cell Res. 2015 Nov;25(11):1219-36. doi: 10.1038/cr.2015.122. Epub 2015 Oct 16.


A structural snapshot of the rhodopsin-arrestin complex.

Kang Y, Gao X, Zhou XE, He Y, Melcher K, Xu HE.

FEBS J. 2016 Mar;283(5):816-21. doi: 10.1111/febs.13561. Epub 2015 Nov 7. Review.


Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling.

Zhang F, Yao J, Ke J, Zhang L, Lam VQ, Xin XF, Zhou XE, Chen J, Brunzelle J, Griffin PR, Zhou M, Xu HE, Melcher K, He SY.

Nature. 2015 Sep 10;525(7568):269-73. doi: 10.1038/nature14661. Epub 2015 Aug 10.


Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery.

Wu ZS, Cheng H, Jiang Y, Melcher K, Xu HE.

Acta Pharmacol Sin. 2015 Aug;36(8):895-907. doi: 10.1038/aps.2015.66. Review.


Structural basis of the Norrin-Frizzled 4 interaction.

Shen G, Ke J, Wang Z, Cheng Z, Gu X, Wei Y, Melcher K, Xu HE, Xu W.

Cell Res. 2015 Sep;25(9):1078-81. doi: 10.1038/cr.2015.92. Epub 2015 Jul 31. No abstract available.


Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

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 MH, Zhang C, Moeller A, West GM, Pascal BD, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad CE, 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 JC, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE.

Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22.


Structures and regulation of non-X orphan nuclear receptors: A retinoid hypothesis.

Zhi X, Zhou XE, Melcher K, Xu HE.

J Steroid Biochem Mol Biol. 2016 Mar;157:27-40. doi: 10.1016/j.jsbmb.2015.06.012. Epub 2015 Jul 6. Review.


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