Biophysics

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

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics

1. Nicholas James Ose
2. Paul Campitelli
3. Tushar Modi
4. I Can Kazan
5. Sudhir Kumar
6. Sefika Banu Ozkan

• Curated by eLife

  eLife assessment

  This important study investigates various variants of the SARS-COV-2 spike protein using established computational methods, complemented by experimental validation efforts. The evidence, bolstered by an evolutionary approach and protein dynamics, is solid. Placing this research in the broader context of the field could further enrich the manuscript. It will interest biophysicists focused on allostery and protein evolution.

Reviewed by eLife

Mitosis sets nuclear homeostasis of cancer cells under confinement

1. Malèke Mouelhi
2. Alexis Saffon
3. Morgane Roinard
4. Hélène Delanoë-Ayari
5. Sylvain Monnier
6. Charlotte Rivière

• Curated by eLife

  eLife assessment

  This important study describes the new observation that nuclear volume responds to confinement in a manner that requires transit through mitosis. The authors present solid evidence demonstrating that nuclear volume decreases upon nuclear envelope reformation under confinement in a manner that reestablishes a homeostatic state of nuclear envelope tension. Additional experimental support could provide a more complete case for the proposed underlying mechanisms governing this response. The work will be of broad interest to cell biologists and those interested in cell and organismal scaling.

Reviewed by eLife

Dissecting Mechanisms of Ligand Binding and Conformational Changes in the Glutamine-Binding Protein

1. Zhongying Han
2. Sabrina Panhans
3. Sophie Brameyer
4. Ecenaz Bilgen
5. Marija Ram
6. Anna Herr
7. Alessandra Narducci
8. Michael Isselstein
9. Paul D. Harris
10. Oliver Brix
11. Kirsten Jung
12. Don C. Lamb
13. Eitan Lerner
14. Douglas Griffith
15. Thomas R. Weikl
16. Niels Zijlstra
17. Thorben Cordes

• Curated by eLife

  eLife assessment

  This important study combines a range of biophysical techniques to carry out a series of compelling experiments to explore whether glutamine binding protein binds glutamine via an induced fit or a conformational selection process. The evidence supporting the major conclusion of the work is convincing, although it may not be generalized to other protein-ligand or protein-protein systems. The work will be of broad interest to biochemists and biophysicists.

Reviewed by eLife

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