Biophysics

The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide

1. Bing Li
2. Prasanna Suresh
3. Jack Brelstaff
4. Shekhar Kedia
5. Clare E Bryant
6. David Klenerman

• Curated by eLife

  eLife assessment

  This important study uses a novel light sheet imaging technique to investigate how different TLR4 agonists regulate Myddosome formation. The data showing that LPS and A-beta can control the kinetics and size of Myddosome assembly are compelling. This paper should be of substantial interest to the innate immunity field.

Reviewed by eLife

Prediction of Ca ²⁺ Binding Site in Proteins With a Fast and Accurate Method Based on Statistical Mechanics and Analysis of Crystal Structures

1. Abdul Basit
2. Devapriya Choudhury
3. Pradipta Bandyopadhyay

Reviewed by PREreview

A parameterized two-domain thermodynamic model explains diverse mutational effects on protein allostery

1. Zhuang Liu
2. Thomas G Gillis
3. Srivatsan Raman
4. Qiang Cui

• Curated by eLife

  eLife assessment

  The study presents valuable findings where two-domain thermodynamic model for TetR accurately predicts in vivo phenotype changes brought about as a result of various mutations. The evidence provided is compelling and features the first innovative observations with a computational model that captures the structural behavior, much more than the current single-domain models.

Reviewed by eLife

Dependence of nucleosome mechanical stability on DNA mismatches

1. Thuy TM Ngo
2. Bailey Liu
3. Feng Wang
4. Aakash Basu
5. Carl Wu
6. Taekjip Ha

• Curated by eLife

  eLife assessment

  This manuscript reports important data on the stability of nucleosomes with dsDNA substrates containing defined mismatches at three defined nucleosomal positions. Compelling evidence obtained by single-molecule FRET experiments shows that certain mismatches lead to more stable nucleosomes likely because mismatches kink to enhance DNA flexibility leading to higher nucleosome stability. The biological significance and implications of the findings remain unclear.

Reviewed by eLife

The French flag problem revisited: Creating robust and tunable axial patterns without global signaling

1. Stephan Kremser
2. Gabriel Vercelli
3. Ulrich Gerland

• Curated by eLife

  eLife assessment

  This important study uses cellular automata and evolution algorithms to offer an alternative to long-range signalling models of developmental patterning. The computational evidence that local rules suffice to produce a robust and global pattern is convincing. With some additional insights that connect the theoretical findings back to real biological examples, this work could be of interest to the broad community of developmental and systems biologists.

Reviewed by eLife

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

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

1. Arne Elofsson
2. Ling Han
3. Enrica Bianchi
4. Gavin J Wright
5. Luca Jovine

• Curated by eLife

  eLife assessment

  This study offers valuable insights into the structural architecture of the mammalian egg-sperm fusion synapse, shedding light on the role of specific proteins in fertilization. The significance of the findings lies in the potential identification of a pentameric complex involved in gamete fusion by AlphaFold Multimer. The strength of evidence for the approach/methodology is solid, while the experimental validation is incomplete in supporting these interactions. This work will be of interest to biomedical researchers working on fertility and reproductive health.

Reviewed by eLife

Metric Ion Classification (MIC): A deep learning tool for assigning ions and waters in cryo-EM and x-ray crystallography structures

1. Laura Shub
2. Wenjin Liu
3. Georgios Skiniotis
4. Michael J. Keiser
5. Michael J. Robertson

Reviewed by PREreview

Cyclic muscle contractions reinforce the actomyosin motors and mediate the full elongation of C. elegans embryo

1. Anna Dai
2. Martine Ben Amar

• Curated by eLife

  eLife assessment

  Using continuum theory of elastic solids the authors present evidence that periodic muscle contraction leads to elongation of C. elegans embryos by storing elastic energy that is subsequently released by extending the embryo's long axis. This important finding could apply to other developmental processes and be exploited in soft robotics. The presented evidence is convincing on the phenomenological level adopted in the work. How bending energy is converted into elongation on a more microscopic level remains to be worked out.

Reviewed by eLife

The αC-β4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A

1. Cristina Olivieri
2. Yingjie Wang
3. Caitlin Walker
4. Manu Veliparambil Subrahmanian
5. Kim N Ha
6. David Bernlohr
7. Jiali Gao
8. Carlo Camilloni
9. Michele Vendruscolo
10. Susan S Taylor
11. Gianluigi Veglia

• Curated by eLife

  eLife assessment

  This important study provides an example of integrating computational and experimental approaches that lead to new insights into the energy landscape of a model kinase. Compelling use of molecular dynamics simulations and NMR spectroscopy provide a conformational description of active and excited states of the kinase; one of which has not been captured in previously solved crystal structures. Overall, this comprehensive study expands our understanding of the architecture and allosteric features of the conserved bilobal kinase domain structure.

Reviewed by eLife