1. Dynamics of immune memory and learning in bacterial communities

    This article has 2 authors:
    1. Madeleine Bonsma-Fisher
    2. Sidhartha Goyal
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    • Curated by eLife

      eLife assessment

      In this important work, the authors develop a theory for the co-evolutionary dynamics of bacteria and phages, where the major evolutionary pressure comes from CRISPR-Cas adaptive immunity in bacteria. Through extensive stochastic numerical simulations and analytical calculations, the paper presents a compelling analysis of the emergent properties of immune interactions, in the regime of a single proto-spacer and a single spacer. Some of the trends highlighted by the model are recovered from experimental data. The main results concern how diversity in both phage and bacteria population are linked and are shaped by immunity, and should be of broad interest in immunology.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  2. Mechanical basis and topological routes to cell elimination

    This article has 4 authors:
    1. Siavash Monfared
    2. Guruswami Ravichandran
    3. José Andrade
    4. Amin Doostmohammadi
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In this work, Monfared et al. construct a useful three-dimensional phase-field model for cell layers and use this to investigate the link of extrusion events to defects in cellular arrangement. The extension of existing 2D phase field models to three dimensions is an important contribution of this paper. Here the model is used to study the importance of cell-cell and cell-substrate interaction in extrusion from cell monolayers. Their claim that extrusion events can be distinctly linked to defects in nematic and hexatic orders in the monolayer need to be better justified to be fully convincing.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  3. Conformational and oligomeric states of SPOP from small-angle X-ray scattering and molecular dynamics simulations

    This article has 4 authors:
    1. F Emil Thomasen
    2. Matthew J Cuneo
    3. Tanja Mittag
    4. Kresten Lindorff-Larsen
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    • Curated by eLife

      eLife assessment

      In this important paper, the authors have developed an approach for simultaneously optimizing the conformational ensemble and degrees of oligomerization, and this has been tested by applying it to a specific protein (SPOP). Comparison of the quality of fits with different models also provides valuable insights into structural features important to the assembly of oligomers. The approach, presented with compelling experimental support, is potentially applicable to other systems as well.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  4. Tracking multiple conformations occurring on angstrom-and-millisecond scales in single amino-acid-transporter molecules

    This article has 3 authors:
    1. Yufeng Zhou
    2. John H Lewis
    3. Zhe Lu
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    • Curated by eLife

      eLife assessment

      This paper presents a single-molecule polarization microscopy study aimed at monitoring the arginine/agmatine antiporter AdiC as it transiently exchanges between conformational states. This approach measures how a bis-TMR fluorophore anchored onto helix 6a changes its orientation in the microscope, and the authors identify four states that they propose correspond to the key steps in the transport cycle (inward-open, inward occluded, outward occluded and outward open). This is a cutting-edge and challenging approach that sets the stage for direct measurements of conformational equilibria and will thus be of interest to anyone studying transport mechanisms. However, additional investigation is required to validate the robustness of the post-processing of the single-molecule data to yield the four-state model compared to alternate models, to test the robustness of the data with transport mutants/conditions that would slow or eliminate states, and to consolidate transitions that are observed that conflict with previous observations of obligatory coupling in AdiC.

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  5. State-specific morphological deformations of the lipid bilayer explain mechanosensitive gating of MscS ion channels

    This article has 5 authors:
    1. Yein Christina Park
    2. Bharat Reddy
    3. Navid Bavi
    4. Eduardo Perozo
    5. José D Faraldo-Gómez
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    • Curated by eLife

      eLife assessment

      The manuscript reports a new structure of the small conductance mechanosensitive channel MscS from E. coli in the open state, together with coarse-grained and atomistic molecular dynamics simulations of MscS and the related channel MSL1 of plant mitochondria in closed and open states. The important finding is that the surrounding lipid bilayer is severely distorted in the closed state only, with the protein inducing high curvature in the inner leaflet due to the membrane protruding into the cytoplasm. The authors argue convincingly that the role of membrane tension is to increase the energy of the protein-membrane system in this closed state compared to the relatively flat-membrane open state, in contrast to the previous proposal that tension-induced gating is driven by expansion of the in-plane area of the protein. The finding may be relevant for the understanding of ion channel mechano-sensation more generally, including of the PIEZO1 channel.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  6. Evolutionary divergence in the conformational landscapes of tyrosine vs serine/threonine kinases

    This article has 4 authors:
    1. Joan Gizzio
    2. Abhishek Thakur
    3. Allan Haldane
    4. Ronald M Levy
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    • Curated by eLife

      eLife assessment

      This important paper provides a convincing mechanism for relative binding specificity of Type II inhibitors to kinases. The combination of a sequence-derived Potts-model with experimental dissociation constants and calculated free energies of binding to the DFG-out state is highly compelling and goes beyond the current state of the art. Given the importance of kinases in pathophysiological processes, the results will be of interest to a broad audience and, in addition, the combination of computational methods can be applicable to a wide variety of other biophysical processes that involve conformational rearrangements.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  7. Calcium dependence of both lobes of calmodulin is involved in binding to a cytoplasmic domain of SK channels

    This article has 3 authors:
    1. David B Halling
    2. Ashley E Philpo
    3. Richard W Aldrich
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    • Curated by eLife

      eLife assessment

      This manuscript provides compelling evidence that in response to calcium, the C-lobe of calmodulin changes its interaction with the C-terminal domain of an SK2 small-conductance calcium-activated potassium channel. These findings will be of interest to those in the field of ion channels and calcium signaling as they are valuable to understanding the molecular mechanics by which calcium activates SK2 channels, which are important for a wide variety of physiological signaling processes.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  8. Molecular mechanism underlying desensitization of the proton-activated chloride channel PAC

    This article has 7 authors:
    1. James Osei-Owusu
    2. Zheng Ruan
    3. Ljubica Mihaljević
    4. Daniel S Matasic
    5. Kevin Hong Chen
    6. Wei Lü
    7. Zhaozhu Qiu
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    • Curated by eLife

      eLife assessment

      This valuable work, of interest to ion channel physiologists, identifies regions involved in the desensitization of the proton-activated chloride channel (PAC), a widely expressed ion channel involved in organelle pH homeostasis and acid-induced cell death. At the present stage the data only incompletely support the interpretations, and further experiments will be required to consolidate some of the authors' claims.

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  9. A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0

    This article has 12 authors:
    1. Jasenko Zivanov
    2. Joaquín Otón
    3. Zunlong Ke
    4. Andriko von Kügelgen
    5. Euan Pyle
    6. Kun Qu
    7. Dustin Morado
    8. Daniel Castaño-Díez
    9. Giulia Zanetti
    10. Tanmay AM Bharat
    11. John AG Briggs
    12. Sjors HW Scheres
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    • Curated by eLife

      eLife assessment

      Single-particle tomography (SPT) is a useful method to determine the structure of proteins imaged in situ. This important work presents an easy-to-use tool for SPT that approximates the use of 2D tomographic projections using a "pseudo-subtomogram" data structure, chosen to facilitate implementation within the existing Relion codebase. The examples shown provide solid support for the claims about the efficacy of the approach.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  10. Conserved allosteric inhibition mechanism in SLC1 transporters

    This article has 9 authors:
    1. Yang Dong
    2. Jiali Wang
    3. Rachel-Ann Garibsingh
    4. Keino Hutchinson
    5. Yueyue Shi
    6. Gilad Eisenberg
    7. Xiaozhen Yu
    8. Avner Schlessinger
    9. Christof Grewer
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    • Curated by eLife

      eLife assessment

      The goal of this study is to identify allosteric modulators of a SLC-1 amino acid transporter, ASCT2, which has been implicated in cancer progression. By combining computational and docking methods with functional measurements, this study provides solid evidence for specific aspects of allosteric SLC-1 inhibition mechanisms. The findings are important to transporter mechanism and pharmacology.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
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