1. Salmonids elicit an acute behavioral response to heterothermal environments

    This article has 7 authors:
    1. Robert Naudascher
    2. Stefano Brizzolara
    3. Jonasz Slomka
    4. Robert M. Boes
    5. Markus Holzner
    6. Luiz G. M. Silva
    7. Roman Stocker
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable paper investigates how fish avoid thermal disturbances that occur on fast timescales. The authors use a creative experimental approach that quickly creates a vertical thermal interface, which they combine with careful behavioral analyses. The evidence supporting their results is solid, but there is a potential confounding factor between temperature and vertical positioning, and characterization of the thermal interface would greatly assist in interpreting the results.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  2. Decoding Phase Separation of Prion-Like Domains through Data-Driven Scaling Laws

    This article has 6 authors:
    1. M Julia Maristany
    2. Anne Aguirre Gonzalez
    3. Jorge R Espinosa
    4. Jan Huertas
    5. Rosana Collepardo-Guevara
    6. Jerelle A Joseph
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The authors performed extensive coarse-grained molecular dynamics simulations of 140 different prion-like domain variants to interrogate how specific amino acid substitutions determine the driving forces for phase separation. The analyses are solid, and the predictive scaling laws can aid in identifying potential phase-separating regions in uncharacterized proteins. Overall, this is a valuable contribution to the field of biomolecular condensates. It exemplifies how data-driven methodologies can uncover new insights into complex biological phenomena.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  3. Ligand-Coupled Conformational Changes in a Cyclic Nucleotide-Gated Ion Channel Revealed by Time-Resolved Transition Metal Ion FRET

    This article has 3 authors:
    1. Pierce Eggan
    2. Sharona E Gordon
    3. William N Zagotta
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful study uses fluorescence lifetime imaging (FLIM) and tmFRET to resolve resting vs. active conformational heterogeneity and free energy differences driven by cGMP and cAMP in a tetrameric arrangement of isolated CNBDs from a prokaryotic CNG channel. The data are compelling and the experimental approach features rigorous new methods and analyses. Limitations include (1) only the cytosolic fragments of the channel were studied; (2) the results are not adequately discussed in the context of the extensive prior literature about conformational dynamics and energetics of CNBD-containing ion channels; (3) ambiguity in the stoichiometry of labeled:unlabeled subunits; and (4) the lack of a discussion of alternative interpretations of the data. The study will be of interest to scientists working on the structural mechanisms of membrane proteins.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  4. Atomistic Tuning of the GeoCas9 Recognition Lobe Modulates Allosteric Motions and Guide RNA Interactions

    This article has 7 authors:
    1. Helen B Belato
    2. Alexa L Knight
    3. Alexandra M D’Ordine
    4. Zhiqiang Fan
    5. Jinping Luo
    6. Gerwald Jogl
    7. George P Lisi
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study provides useful insights into the conformational dynamics of the nucleic acid recognition lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. The influence of local dynamics and allosteric regulation on guide RNA binding affinity and DNA cleavage specificity is investigated via cutting-edge NMR approaches and mutagenesis. While backed by rigorous biophysical analyses, evidence supporting the proposed mechanistic model is found to be incomplete due to the limited impact of the studied mutations on GeoCas9 cleavage activity. This work will be of interest to biochemists and biophysicists interested in interdomain communication and allosteric mechanisms in Cas9 enzymes.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  5. Decoupling of the Onset of Anharmonicity between a Protein and Its Surface Water around 200 K

    This article has 11 authors:
    1. Lirong Zheng
    2. Bingxin Zhou
    3. Banghao Wu
    4. Yang Tan
    5. Juan Huang
    6. Madhusudan Tyagi
    7. Victoria García Sakai
    8. Takeshi Yamada
    9. Hugh O’Neill
    10. Qiu Zhang
    11. Liang Hong
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The study answers the important question of whether the conformational dynamics of proteins are slaved by the motion of solvent water or are intrinsic to the polypeptide. The results from neutron scattering experiments, involving isotopic labelling, carried out on a set of four structurally different proteins are convincing, showing that protein motions are not coupled to the solvent. A strength of this work is the study of a set of proteins using spectroscopy covering a range of resolutions. A minor weakness is the limited description of computational methods and analysis of data. The work is of broad interest to researchers in the fields of protein biophysics and biochemistry.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 1 listLatest version Latest activity
  6. Membrane curvature sensing and symmetry breaking of the M2 proton channel from Influenza A

    This article has 5 authors:
    1. Cole V. M. Helsell
    2. Frank V. Marcoline
    3. James Lincoff
    4. Andrew M. Natale
    5. Michael Grabe
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The authors combined atomistic simulations and continuum mechanics models to probe how structural features of the M2 channel impact the local membrane properties and stability of the channel in membranes of different curvatures. The insights gained in this work can potentially lead to novel strategies that screen for drug molecules that stabilize fission-incompetent conformations of the M2 channel. The multi-scale computational approach will find utility to many problems in membrane reshaping.

      (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.)

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    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  7. Conservation of the cooling agent binding pocket within the TRPM subfamily

    This article has 3 authors:
    1. Kate Huffer
    2. Elisabeth V Oskoui
    3. Kenton J Swartz
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In this valuable study, Huffer et al posit that non-cold sensing members of the TRPM subfamily of ion channels (e.g., TRPM2, TRPM4, TRPM5) contain a binding pocket for icilin that overlaps with the one found in the cold-activated TRPM8 channel. By examining a body of TRP channel cryo-EM structures to identify the conserved site, this study presents convincing electrophysiological evidence supporting the identification of an icilin binding pocket within TRPM4. This study shows that icilin has modulatory effects on the TRPM4 channel and will be of direct interest to those working in the TRP-channel field, but it also has implications for studies of somatosensation, taste, as well as pharmacological targeting of the TRPM subfamily.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  8. Revealing a hidden conducting state by manipulating the intracellular domains in KV10.1 exposes the coupling between two gating mechanisms

    This article has 4 authors:
    1. Reham Abdelaziz
    2. Adam P Tomczak
    3. Andreas Neef
    4. Luis A Pardo
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable study examines the role of the interaction between cytoplasmic N- and C-terminal domains in voltage-dependent gating of Kv10.1 channels. The authors claim to have identified a hidden open state in Kv10.1 mutant channels, thus providing a window for observing early conformational transitions associated with channel gating. The evidence supporting the major conclusions is incomplete, however, and additional work is required to determine the molecular mechanism underlying the observations in this study. With the experimental conditions clarified and the mechanistic interpretations addressed, this work could be significant in understanding the gating mechanisms of the KCNH family and will appeal to biophysicists interested in ion channels and physiologists interested in cancer biology.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  9. Modulation of α-Synuclein Aggregation Amid Diverse Environmental Perturbation

    This article has 3 authors:
    1. Abdul Wasim
    2. Sneha Menon
    3. Jagannath Mondal
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study provides important biophysical insights into the molecular mechanism underlying the association of alpha-synuclein chains, which is essential for understanding the pathogenesis of Parkinson's disease. The data analysis is solid, and the methodology can help investigate other molecular processes involving intrinsically disordered proteins.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 1 listLatest version Latest activity
  10. Differential conformational dynamics in two type-A RNA-binding domains drive the double-stranded RNA recognition and binding

    This article has 5 authors:
    1. Firdousi Parvez
    2. Devika Sangpal
    3. Harshad Paithankar
    4. Zainab Amin
    5. Jeetender Chugh
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents a useful comparison of the dynamic properties of two RNA-binding domains. The data collection and analysis are solid, making excellent use of a suite of NMR experiments and ITC data. Nonetheless, reported evidence was found to only partially support the proposed connection between the backbone dynamics of the tandem domains and their RNA binding activity. This work will be of interest to biophysicists working on RNA-binding proteins.

    Reviewed by eLife

    This article has 8 evaluationsAppears in 1 listLatest version Latest activity