Biophysics

Divergent mechanisms of steroid inhibition in the human ρ1 GABA _A receptor

1. Chen Fan
2. John Cowgill
3. Rebecca J. Howard
4. Erik Lindahl

Reviewed by PREreview

High-throughput discovery of inhibitory protein fragments with AlphaFold

1. Andrew Savinov
2. Sebastian Swanson
3. Amy E. Keating
4. Gene-Wei Li

Reviewed by PREreview

Liquid-like condensates that bind actin drive filament polymerization and bundling

1. Caleb Walker
2. Aravind Chandrasekaran
3. Daniel Mansour
4. Kristin Graham
5. Andrea Torres
6. Liping Wang
7. Eileen M. Lafer
8. Padmini Rangamani
9. Jeanne C. Stachowiak

Reviewed by Arcadia Science

Microphase separation produces interfacial environment within diblock biomolecular condensates

1. Andrew P Latham
2. Longchen Zhu
3. Dina A Sharon
4. Songtao Ye
5. Adam P Willard
6. Xin Zhang
7. Bin Zhang

• Curated by eLife

  eLife assessment

  This important study investigates the structural organization of a series of diblock elastin-like polypeptide condensates. The methodology is highly compelling, as it combines multiscale simulations and fluorescence lifetime imaging microscopy experiments. The results increase our understanding of model biomolecular condensates.

Reviewed by eLife

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