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  2. Structural insights into the orthosteric inhibition of P2X receptors by non-ATP analog antagonists

    1. Danqi Sheng
    2. Chen-Xi Yue
    3. Fei Jin
    4. Yao Wang
    5. Muneyoshi Ichikawa
    6. Ye Yu
    7. Chang-Run Guo
    8. Motoyuki Hattori

    • Curated by eLife

      eLife assessment

      This study by Sheng and colleagues provides valuable insights into the mechanism of competitive inhibitors of P2X receptors. The structural and functional evidence supporting the subtype specificity of pyridoxal-5'-phosphate derivatives is compelling and provides information for designing drugs that selectively target different subtypes of P2X receptor channels. The work will be of interest to biochemists, structural biologists, and pharmacologists.

    Reviewed by eLife

    7 evaluationsAppears in 2 listsLatest version Latest activity

  3. Conformational dynamics of a nicotinic receptor neurotransmitter site

    1. Mrityunjay Singh
    2. Dinesh C Indurthi
    3. Lovika Mittal
    4. Anthony Auerbach
    5. Shailendra Asthana

    • Curated by eLife

      eLife Assessment

      This useful work provides insight into agonist binding to nicotinic acetylcholine receptors, which is the stimulus for channel activation that regulates muscle contraction at the neuromuscular junction. The authors use in silico methods to explore the transient conformational change from a low to high affinity agonist-bound conformation as occurs during channel opening, but for which structural information is lacking owing to its transient nature. The simulations indicating that ligands flip ~180 degrees in the binding site as it transitions from a low to high affinity bound conformation are solid. A limitation is the approximation of binding energies using Poisson-Boltzmann Surface Area and mismatch between calculated and experimental binding energies for two of the four ligands tested. Nonetheless, this work presents an intriguing picture for the nature of a transient conformational change at the agonist binding site correlated with channel opening.

    Reviewed by eLife

    17 evaluationsAppears in 2 listsLatest version Latest activity

  6. Structural and mechanistic insights into human choline and ethanolamine transport

    1. Keiken Ri
    2. Tsai-Hsuan Weng
    3. Ainara Claveras Cabezudo
    4. Wiebke Jösting
    5. Zhang Yu
    6. Andre Bazzone
    7. Nancy C.P. Leong
    8. Sonja Welsch
    9. Raymond T. Doty
    10. Gonca Gursu
    11. Tiffany Jia Ying Lim
    12. Sarah Luise Schmidt
    13. Janis L. Abkowitz
    14. Gerhard Hummer
    15. Di Wu
    16. Long N Nguyen
    17. Schara Safarian
    Appears in 1 listLatest version

  8. Structure-based discovery of CFTR potentiators and inhibitors

    1. Fangyu Liu
    2. Anat Levit Kaplan
    3. Jesper Levring
    4. Jürgen Einsiedel
    5. Stephanie Tiedt
    6. Katharina Distler
    7. Natalie S. Omattage
    8. Ivan S. Kondratov
    9. Yurii S. Moroz
    10. Harlan L. Pietz
    11. John J. Irwin
    12. Peter Gmeiner
    13. Brian K. Shoichet
    14. Jue Chen
    Appears in 1 listLatest version

  9. Human pannexin 1 channel is not phosphorylated by Src tyrosine kinase at Tyr199 and Tyr309

    1. Zheng Ruan
    2. Junuk Lee
    3. Yangyang Li
    4. Juan Du
    5. Wei Lü

    • Curated by eLife

      eLife assessment

      The current manuscript re-examines an established claim in the literature that human PANX-1 is regulated by Src kinase phosphorylation at two tyrosine residues, Y199 and Y309. This issue is important for our understanding of Pannexin channel regulation. The authors present an extensive series of experiments that fail to detect PANX-1 phosphorylation at these sites. Although the authors' approach is more rigorous than the previous studies, this work relies primarily on negative results that are not unambiguously definitive; the work nonetheless provides a compelling reason for the field to reexamine conclusions drawn in earlier studies.

    Reviewed by eLife

    9 evaluationsAppears in 2 listsLatest version Latest activity

  13. Negative allosteric modulation of the µ-opioid receptor

    1. Evan S. O’Brien
    2. Vipin Ashok Rangari
    3. Amal El Daibani
    4. Shainnel O. Eans
    5. Betsy White
    6. Haoqing Wang
    7. Yuki Shiimura
    8. Kaavya Krishna Kumar
    9. Kevin Appourchaux
    10. Weijiao Huang
    11. Chensong Zhang
    12. Jesper M. Mathiesen
    13. Tao Che
    14. Jay P. McLaughlin
    15. Susruta Majumdar
    16. Brian K. Kobilka
    Appears in 1 listLatest version

  15. Structural mechanisms for VMAT2 inhibition by tetrabenazine

    1. Michael P Dalton
    2. Mary Hongying Cheng
    3. Ivet Bahar
    4. Jonathan A Coleman

    • Curated by eLife

      eLife assessment

      The report presents the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to tetrabenazine, a clinical drug. VMAT2 is critical for neurotransmission, and the study constitutes an important milestone in neurotransmitter transport research. The evidence presented in the report is convincing and provides new opportunities for developing improved therapeutic interventions and furthering our understanding of this vital protein's function.

    Reviewed by eLife

    15 evaluationsAppears in 2 listsLatest version Latest activity

  16. Structural mechanisms for VMAT2 inhibition by tetrabenazine

    1. Michael P Dalton
    2. Mary Hongying Cheng
    3. Ivet Bahar
    4. Jonathan A Coleman

    • Curated by eLife

      eLife assessment

      The report presents the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to tetrabenazine, a clinical drug. VMAT2 is critical for neurotransmission, and the study constitutes an important milestone in neurotransmitter transport research. The evidence presented in the report is convincing and provides new opportunities for developing improved therapeutic interventions and furthering our understanding of this vital protein's function.

    Reviewed by eLife

    15 evaluationsAppears in 2 listsLatest version Latest activity

  18. LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction

    1. Colin H Peters
    2. Rohit K Singh
    3. Avery A Langley
    4. William G Nichols
    5. Hannah R Ferris
    6. Danielle A Jeffrey
    7. Catherine Proenza
    8. John R Bankston

    • Curated by eLife

      eLife assessment

      This study identifies the molecular determinants of LRMP co-regulation of HCN 4 activity. The evidence supporting the conclusions, which is compelling, is backed by rigorous electrophysiological and spectroscopic analysis. The work is important because it greatly enhances our understanding of the mechanisms of HCN channel regulation in a tissue-specific manner and highlights a functional role for more disordered regions that have yet to be structurally resolved.

    Reviewed by eLife

    9 evaluationsAppears in 2 listsLatest version Latest activity

  20. Step-wise activation of a Family C GPCR

    1. Kaavya Krishna Kumar
    2. Haoqing Wang
    3. Chris Habrian
    4. Naomi R. Latorraca
    5. Jun Xu
    6. Evan S. O’Brien
    7. Chensong Zhang
    8. Elizabeth Montabana
    9. Antoine Koehl
    10. Susan Marqusee
    11. Ehud Y. Isacoff
    12. Brian K. Kobilka
    Appears in 1 listLatest version
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