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  3. Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels

    1. Michaela A Edmond
    2. Andy Hinojo-Perez
    3. Xiaoan Wu
    4. Marta E Perez Rodriguez
    5. Rene Barro-Soria

    • Curated by eLife

      Evaluation Summary:

      This study investigates the mechanism of voltage-dependent activation of the KCNQ class of potassium channels that regulate neuronal firing, and are mutated in monogenic forms of epilepsy. This study makes an important technical step forward by reporting measurements of voltage-dependent conformational changes of KCNQ2/Kv7.2 channels, measurements which are known to be extremely difficult for this biologically important channel. Understanding these conformational changes allows the authors to investigate models of how voltage-dependent changes are coupled to opening of the channel pore, and also identify diverse mechanisms by which disease-linked mutations of KCNQ2/Kv7.2 may alter channel function.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife

    5 evaluationsAppears in 2 listsLatest version Latest activity

  7. Ancestral acetylcholine receptor ÎČ-subunit forms homopentamers that prime before opening spontaneously

    1. Christian JG Tessier
    2. Raymond M Sturgeon
    3. Johnathon R Emlaw
    4. Gregory D McCluskey
    5. F Javier PĂ©rez-Areales
    6. Corrie JB daCosta

    • Curated by eLife

      Evaluation Summary:

      This paper will be of interest to readers interested ligand-gated ion channels and their evolution. The authors show that ancestral AChR beta subunits reconstructed phylogenetically can form homomeric channels that open spontaneously. The work expands our understanding of agonist-independent AChR gating and highlights intriguing aspects of AChR evolution.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

    Reviewed by eLife

    4 evaluationsAppears in 2 listsLatest version Latest activity

  10. Ligand bias underlies differential signaling of multiple FGFs via FGFR1

    1. Kelly Karl
    2. Nuala Del Piccolo
    3. Taylor Light
    4. Tanaya Roy
    5. Pooja Dudeja
    6. Vlad-Constantin Ursachi
    7. Bohumil Fafilek
    8. Pavel Krejci
    9. Kalina Hristova

    • Curated by eLife

      eLife assessment

      This manuscript describes useful data on the mechanisms underlying the activation of the receptor tyrosine kinase FGFR1 and stimulation of intracellular signaling pathways in response to FGF4, FGF8, or FGF9 binding to the extracellular domain of FGFR1. Solid evidence for quantitative differences in the downstream responses induced by the three ligands is presented. This manuscript will be of interest to biochemists and cell biologists working on receptor tyrosine kinases and general cell signalling across membranes.

    Reviewed by eLife

    8 evaluationsAppears in 2 listsLatest version Latest activity

  11. Cryo-EM structure of the human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand-binding specificity

    1. Yunseok Heo
    2. Eojin Yoon
    3. Ye-Eun Jeon
    4. Ji-Hye Yun
    5. Naito Ishimoto
    6. Hyeonuk Woo
    7. Sam-Yong Park
    8. Ji-Joon Song
    9. Weontae Lee

    • Curated by eLife

      Evaluation Summary:

      This manuscript reports the cryoEM structure of somatostatin receptor 2 (SSTR2) bound to its agonist SST-14 and a heterotrimeric G protein. In addition to presenting the structure itself, the authors include discussion and analysis of ligand recognition and subtype specificity, guided by AlphaFold2 modeling of other somatostatin receptor subtypes. Additional functional data to test the importance of proposed receptor-ligand contacts will be critical to understanding which of the features directly contribute to subtype specificity. Because somatostatin signaling is important in endocrine biology, including in diseases such as acromegaly and some cancers, the work should in principle be of interest to a broad audience.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Reviewed by eLife

    3 evaluationsAppears in 2 listsLatest version Latest activity