Biophysics

ATP binding facilitates target search of SWR1 chromatin remodeler by promoting one-dimensional diffusion on DNA

1. Claudia C Carcamo
2. Matthew F Poyton
3. Anand Ranjan
4. Giho Park
5. Robert K Louder
6. Xinyu A Feng
7. Jee Min Kim
8. Thuc Dzu
9. Carl Wu
10. Taekjip Ha

• Curated by eLife

  Evaluation Summary:

  Using biophysical measurements, this work establishes that the SWR1 chromatin remodeling complex, which directs incorporation of the histone variant H2A.Z adjacent to nucleosome depleted regions, preferentially associates with longer DNA fragments. It is proposed that larger stretches of free DNA determine the specificity of the complex in vivo. These findings will be of general interest to researchers interested in understanding how chromatin remodelling enzymes act to influence the localisation of histone variants.

  (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, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Tonic inhibition of the chloride/proton antiporter ClC-7 by PI(3,5)P2 is crucial for lysosomal pH maintenance

1. Xavier Leray
2. Jacob K Hilton
3. Kamsi Nwangwu
4. Alissa Becerril
5. Vedrana Mikusevic
6. Gabriel Fitzgerald
7. Anowarul Amin
8. Mary R Weston
9. Joseph A Mindell

• Curated by eLife

  Evaluation Summary:

  The focus of the manuscript is the lysosomal Cl-/H+ transporter CLC-7. The main finding is the direct regulation of CLC-7 by PI(3,5)P2, which keeps CLC-7 inactive. This finding may explain the lysosomal and cellular phenotype of a newly identified gain-of-function mutation in CLC-7 that causes lysosomal hyperacidification and large vacuoles.

  (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 #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

All-atom molecular dynamics simulations of Synaptotagmin-SNARE-complexin complexes bridging a vesicle and a flat lipid bilayer

1. Josep Rizo
2. Levent Sari
3. Yife Qi
4. Wonpil Im
5. Milo M Lin

• Curated by eLife

  Evaluation Summary:

  This study investigates the release machinery of synaptic vesicles prior to SNARE-mediated fusion using atomistically detailed molecular dynamics simulations. While the approach provides an unparalleled perspective on a complex process that has eluded direct experimental access, the physiological relevance of the conclusions is not clear yet because of the short duration and necessary molecular approximations and assumptions underlying the simulations. The work will be of interest to all who study vesicle fusions.

  (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 #2 agreed to share their name with the authors.)

Reviewed by eLife

Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors

1. Nanako Atsumi
2. Keiko Yasumatsu
3. Yuriko Takashina
4. Chiaki Ito
5. Norihisa Yasui
6. Robert F Margolskee
7. Atsuko Yamashita

• Curated by eLife

  eLife assessment

  This fundamental study presents solid evidence for T1r (sweet /umami) taste receptors as chloride (Cl-) receptors, based on a combination of state-of-the-art techniques to demonstrate that T1r receptors from Medaka fish bind chloride and that this binding induces a conformational change in the heteromeric receptor. This conformational change leads to low-concentration chloride-specific action potential firing in nerves from neurons containing these receptors in mice, results that represent an important advance in our understanding of the logic of taste perception.

• Curated by Biophysics Colab

  Endorsement statement (17 November 2022)

  The preprint by Atsumi et al. describes how chloride binding to sweet- and umami-sensing proteins (T1R taste receptors) can evoke taste sensation. The authors use an elegant combination of structural, biophysical and electrophysiological approaches to locate a chloride binding site in the ligand-binding domain of medaka fish T1r2a/3 receptors. They convincingly show that low mM concentrations of chloride induce conformational changes and, using single fiber recordings, establish that mouse chorda tympani nerves are activated by chloride in a T1R-dependent manner. This suggests that chloride binding to sweet receptors could mediate the commonly reported sweet taste sensation following ingestion of low concentrations of table salt. The findings will be of broad relevance to those studying taste sensation and ligand recognition in GPCRs.

  (This endorsement by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

Reviewed by eLife, Biophysics Colab

Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers

1. Vladislav Belyy
2. Iratxe Zuazo-Gaztelu
3. Andrew Alamban
4. Avi Ashkenazi
5. Peter Walter

• Curated by eLife

  Evaluation Summary:

  The manuscript reports on a new technical advance in fluorescence microscopy with which changes in the oligomerization of an integral membrane protein can be measured in live cells. The method is used to define the initial steps during activation of the IRE1 signaling arm of the unfolded protein response, leading to the discovery that IRE1 exists as a stable dimer in the absence of stress - which is in contrast to inferences from prior work. In response to stress, the protein assembles into a higher-order oligomer (likely a tetramer), an event that is mediated by the IRE lumenal domain and serves as a prelude to autophosphorylation. While the work will be widely noticed and excitedly discussed in the community, a reconciliation between the different results obtained in this study and in prior work, some of which was reported previously by the same lab, is currently lacking.

  (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

Hijacking of Cellular Functions by Severe Acute Respiratory Syndrome Coronavirus-2. Permeabilization and Polarization of the Host Lipid Membrane by Viroporins

1. Emmanuelle Bignon
2. Marco Marazzi
3. Antonio Monari

Reviewed by ScreenIT

Seipin transmembrane segments critically function in triglyceride nucleation and lipid droplet budding from the membrane

1. Siyoung Kim
2. Jeeyun Chung
3. Henning Arlt
4. Alexander J Pak
5. Robert V Farese
6. Tobias C Walther
7. Gregory A Voth

• Curated by eLife

  Evaluation Summary:

  Kim et al. investigate interactions between Seipin transmembrane domains and triacylglycerol using molecular dynamics simulations. They identify the leading steps in droplet formation and provide a physical basis for understanding the initial phases of this process, highlighting the importance of transmembrane helices in the function of seipin protein. This paper will be of interest to cell biologists and biophysicists aiming to unveil and understand how lipid droplets are formed inside cells. The topic is important given that lipid droplets are key organelles used for energy storage, and that the failure in their formation can result in various metabolic diseases.

  (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

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.1 and BA.2 variants and their mouse origins

1. Youwei Xu
2. Canrong Wu
3. Xiaodan Cao
4. Chunyin Gu
5. Heng Liu
6. Mengting Jiang
7. Xiaoxi Wang
8. Qingning Yuan
9. Kai Wu
10. Jia Liu
11. Deyi Wang
12. Xianqing He
13. Xueping Wang
14. Su-Jun Deng
15. H. Eric Xu
16. Wanchao Yin

Reviewed by ScreenIT

Hierarchical Computational Modeling and Dynamic Network Analysis of Allosteric Regulation in the SARS-CoV-2 Spike Omicron Trimer Structures: Omicron Mutations Cooperate to Allosterically Control Balance of Protein Stability and Conformational Adaptability

1. Gennady M. Verkhivker
2. Steve Agajanian
3. Ryan Kassab
4. Keerthi Krishnan

Reviewed by ScreenIT

The importance of intermediate filaments in the shape maintenance of myoblast model tissues

1. Irène Nagle
2. Florence Delort
3. Sylvie Hénon
4. Claire Wilhelm
5. Sabrina Batonnet-Pichon
6. Myriam Reffay

• Curated by eLife

  Evaluation Summary:

  Nagle and colleagues studied the determinants of key physical properties of multicellular assemblies, using magnetic flattening of spheroids. Their key and insightful result is that intermediate filaments could also be implicated in the setting the elastic properties of these assemblies, shedding light on this central cellular component and how their modifications could be important to the understanding of some pathologies. The paper would be strengthened by additional experiments to better support the claims.

  (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 #2 agreed to share their name with the authors.)

Reviewed by eLife