Biophysics

Adsorption of pulmonary and exogeneous surfactants on SARS-CoV-2 spike protein

1. Kolattukudy P. Santo
2. Alexander V. Neimark

Reviewed by ScreenIT

Excitatory and inhibitory D-serine binding to the NMDA receptor

1. Remy A Yovanno
2. Tsung Han Chou
3. Sarah J Brantley
4. Hiro Furukawa
5. Albert Y Lau

• Curated by eLife

  Evaluation Summary:

  Activation of NMDA receptors requires two co-agonists: Glutamate which binds to the GluN2 subunit and glycine/D-serine which binds to the GluN1 subunit. In the present manuscript, the authors address the interaction of D-serine, which is a less studied co-agonist than glycine, with the GluN1 and GluN2A subunits using molecular simulations as well as electrophysiology experiments. Surprisingly they find that D-serine interacts with the GluN2 subunit, further expanding our molecular understanding of NMDA receptor structure-function.

  (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

SARS-CoV-2 Main Protease: a Kinetic Approach

1. Thierry Rebetez

Reviewed by ScreenIT

Transient exposure of a buried phosphorylation site in an autoinhibited protein

1. Simone Orioli
2. Carl G. Henning Hansen
3. Kresten Lindorff-Larsen

• Curated by eLife

  Evaluation Summary:

  The manuscript describes a metadynamics simulation-based characterization of the binding and unbinding dynamics of a buried phosphorylated residue in the inhibitory module to the functional domain of Vav1, in an effort to shed lights on the autoinhibition mechanism. The work led to a conformation-selection scenario of the event. The authors discussed the inconsistency between the computational findings and the NMR data, in terms of the free energy differences between the bound and unbound states. Further justification is required for the somewhat ad hoc choice of three collective variables for the metadynamics simulations, including two that are highly correlated.

  (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 model of microtubule dynamics inhibition by kinesin-4 from the crystal structure of KLP-12 –tubulin complex

1. Shinya Taguchi
2. Juri Nakano
3. Tsuyoshi Imasaki
4. Tomoki Kita
5. Yumiko Saijo-Hamano
6. Naoki Sakai
7. Hideki Shigematsu
8. Hiromichi Okuma
9. Takahiro Shimizu
10. Eriko Nitta
11. Satoshi Kikkawa
12. Satoshi Mizobuchi
13. Shinsuke Niwa
14. Ryo Nitta

• Curated by eLife

  Evaluation Summary:

  Here, Taguchi et al. study a member of the kinesin-4 family of motors, which is important in controlling microtubule length during normal development and maintenance. The authors aim to determine how a member of the kinesin-4 family is able to stabilize the tips of microtubules to suppress both their growth and shrinkage. This paper provides compelling data on KLP-12 by combining in vivo C. elegans work with in vitro single-molecule analysis and structural studies of the motor domain. The structure shows that KLP-12 bends tubulin heterodimers to a level that lies in between the extremes of bending by KIF5B (lattice stabilizer) and KIF2C (lattice destabilizer). This study will be of interest to those in the fields of neuronal development and cytoskeletal dynamics.

  (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

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