Biophysics

Structure of the GOLD-domain seven-transmembrane helix protein family member TMEM87A

1. Christopher M Hoel
2. Lin Zhang
3. Stephen G Brohawn

• Curated by eLife

  eLife assessment

  This work addresses the mechanisms of action of the transmembrane proteins TMEM87A and TMEM87B, which are thought to play a role in protein transport, but have been implicated in other processes as well, such as signaling and acting as mechanosensitive ion channels. The study represents an important advance of the understanding of this poorly characterized family of proteins. While the structure is of low resolution, it is well interpreted, and authors take good advantage of AlphaFold2 to gain insights into potential function. The work is of interest to colleagues studying transporters and ion channels.

Reviewed by eLife

Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer

1. Yang Joon Kim
2. Kaitlin Rhee
3. Jonathan Liu
4. Selene Jeammet
5. Meghan A Turner
6. Stephen J Small
7. Hernan G Garcia

• Curated by eLife

  eLife assessment

  The work by Kim et al., used synthetic constructs in Drosophila to examine the relationship between regulators (activator/repressor) and transcription initiation. By measuring regulator concentrations and the corresponding RNA polymerase initiation rates in different synthetic constructs and using a thermodynamic model, the authors concluded that that higher-order cooperativities between the repressor on adjacent binding sites, and that between the repressor and RNA polymerase are needed to explain the observed response curves in RNA polymerase loading rate. This work targets a challenging question in eukaryotic transcription regulation, where higher-order cooperativity between different molecular components, in addition to simple transcription factor binding and unbinding, is often necessary to account for observed promoter behaviors when multiple elements (repressors, mediators, activators) exist.

Reviewed by eLife

Sublytic gasdermin-D pores captured in atomistic molecular simulations

1. Stefan L Schaefer
2. Gerhard Hummer

• Curated by eLife

  eLife assessment

  This paper will be of interest to cell biologists, structural biologists, and biophysicists studying programmed cell death, membrane transport, and protein-lipid interactions. The simulation data presented offers atomistic detail of how gasdermin-D N-terminal domains assemble on the plasma membrane and trigger the formation of membrane pores which lead to pyroptosis. The study is well designed and the resulting data are rigorously analyzed; however, some clarifications and additional data are required to fully justify the conclusions.

Reviewed by eLife

Improved ANAP incorporation and VCF analysis reveal details of P2X7 current facilitation and a limited conformational interplay between ATP binding and the intracellular ballast domain

1. Anna Durner
2. Ellis Durner
3. Annette Nicke

• Curated by eLife

  eLife assessment

  This manuscript constitutes an important foray into the conformational rearrangements throughout various domains of the notoriously difficult-to-study P2X7 receptor, with a focus on the enigmatic intracellular 'ballast' domain. This is of broad interest to those studying the role of enzymatically active intracellular domains of membrane proteins. The authors provide convincing evidence that the ballast domain is unlikely to undergo major conformational changes upon ATP-induced gating, but additional experimental support is required on the facilitation process and to elucidate the consequences exerted by intracellular factors.

Reviewed by eLife

Direct cell extraction of membrane proteins for structure–function analysis

1. Ieva Drulyte
2. Aspen Rene Gutgsell
3. Pilar Lloris-Garcerá
4. Michael Liss
5. Stefan Geschwindner
6. Mazdak Radjainia
7. Jens Frauenfeld
8. Robin Löving

Reviewed by ASAPbio crowd review

Substrate stiffness impacts early biofilm formation by modulating Pseudomonas aeruginosa twitching motility

1. Sofia Gomez
2. Lionel Bureau
3. Karin John
4. Elise-Noëlle Chêne
5. Delphine Débarre
6. Sigolene Lecuyer

• Curated by eLife

  eLife assessment

  This study connects changes in single-cell twitching motility due to substrate stiffness to multicellular phenotypes. It is likely to have a broad impact on those studying microbiology and multicellular communities as it assesses the influence of single-cell behavior on multicellular processes. However, some of the presented data conflict with previously published literature, raising questions about the nature of these differences.

Reviewed by eLife

Phenotyping single-cell motility in microfluidic confinement

1. Samuel A Bentley
2. Hannah Laeverenz-Schlogelhofer
3. Vasileios Anagnostidis
4. Jan Cammann
5. Marco G Mazza
6. Fabrice Gielen
7. Kirsty Y Wan

• Curated by eLife

  eLife assessment

  This paper reports on the development of an impressive microfluidic platform for the study of motility, and motility transitions, exhibited by single algal cells in circular confinement. Building on previous work that showed a three-state motility repertoire for certain green algae, the present work uses extremely long time series and a variety of physical perturbations to show how those dynamics can be altered by environmental conditions. The work will be of interest to a wide range of scientists studying motility and nonequilibrium dynamics, but its impact would be improved by a more insightful analysis of the voluminous data, with connections to physical principles.

Reviewed by eLife

Direct observation of the conformational states of formin mDia1 at actin filament barbed ends and along the filament

1. Julien Maufront
2. Bérengère Guichard
3. Lu-Yan Cao
4. Aurélie Di Cicco
5. Antoine Jégou
6. Guillaume Romet-Lemonne
7. Aurélie Bertin

Reviewed by Review Commons

Synthetic analysis of chromatin tracing and live-cell imaging indicates pervasive spatial coupling between genes

1. Christopher H Bohrer
2. Daniel R Larson

• Curated by eLife

  eLife Assessment:

  The authors use their expertise in live-cell imaging and mathematical modeling to explore the relationship between chromatin structure, gene positioning and transcriptional co-regulation, using two publicly available datasets encompassing chromatin tracing and transcriptional activity. The resulting analysis reveals a weak association between transcription and proximity, but needs more statistical validation to strengthen the validity of the conclusions. With some clarifications and revisions, several findings, such as coupling of spatiotemporal positioning with activity, in-depth analysis of existing imaging/ChIP-seq datasets, could make this work impactful to both specialists and non-specialists.

  (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 #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Noncovalent antibody catenation on a target surface greatly increases the antigen-binding avidity

1. Jinyeop Song
2. Bo-Seong Jeong
3. Seong-Woo Kim
4. Seong-Bin Im
5. Seonghoon Kim
6. Chih-Jen Lai
7. Wonki Cho
8. Jae U Jung
9. Myung-Ju Ahn
10. Byung-Ha Oh

• Curated by eLife

  eLife Assessment:

  The authors sought to enhance antibody binding to target antigens via reversible catenation, as an alternative to affinity maturation, beginning by computationally establishing parameters under which this type of binding enhancement via avidity effects would occur, and then following up with proof-of-principle experiments. While computational predictions and experiments are in excellent agreement, some controls that would further strengthen data interpretation are lacking. If generally applicable, the approach would accelerate efforts to develop antibodies with enhanced binding potency relative to their progenitors, applicable to any area of research employing antibodies.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife