Biophysics

Structural features of heteromeric channels composed of CALHM2 and CALHM4 paralogs

1. Katarzyna Drożdżyk
2. Martina Peter
3. Raimund Dutzler

• Curated by eLife

  eLife assessment

  In this interesting study, Drożdżyk and colleagues analyze the ability of placental CALHM orthologs to form stable complexes, identifying that CALHM2 and CALHM4 form heterooligomeric channels. The authors then determine cryo-EM structures of heterooligomeric CALHM2 and CALHM4 that reveal a distinct arrangement in which the two orthologs can interact, but preferentially segregate in the channel. This is an important study; the data provide compelling support for the interpretations and overall, the work is clearly described.

Reviewed by eLife

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors

1. Damien M Rasmussen
2. Manny M Semonis
3. Joseph T Greene
4. Joseph M Muretta
5. Andrew R Thompson
6. Silvia Toledo Ramos
7. David D Thomas
8. William CK Pomerantz
9. Tanya S Freedman
10. Nicholas M Levinson

• Curated by eLife

  eLife assessment

  This elegant study presents important findings into how small molecules that were originally developed to inhibit the oncogenic kinase, BRAF, instead trigger activation of this kinase target. Compelling and comprehensive evidence supports a new allosteric model to explain the paradoxical activation. This rigorous work will be of great interest to biochemists, structural biologists, and those working on strategies to inhibit kinases in the context of human disease.

Reviewed by eLife

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