Biophysics

Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously

1. Christian JG Tessier
2. Raymond M Sturgeon
3. Johnathon R Emlaw
4. Gregory D McCluskey
5. F Javier Pérez-Areales
6. Corrie JB daCosta

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to readers interested ligand-gated ion channels and their evolution. The authors show that ancestral AChR beta subunits reconstructed phylogenetically can form homomeric channels that open spontaneously. The work expands our understanding of agonist-independent AChR gating and highlights intriguing aspects of AChR evolution.

  (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

Aminomethanesulfonic acid illuminates the boundary between full and partial agonists of the pentameric glycine receptor

1. Josip Ivica
2. Hongtao Zhu
3. Remigijus Lape
4. Eric Gouaux
5. Lucia G Sivilotti

• Curated by eLife

  Evaluation Summary:

  Ivica et al. provide both functional and structural characterization of a relatively unstudied glycine receptor agonist that is structurally in between a full and partial agonist. The combination of cryogenic electron microscopy and electrophysiological approaches allows for complementary structural and functional investigations into the criteria that determine ligand efficacy at the glycine receptor. This manuscript will be of interest to both biophysical and pharmacological investigations of ligand-gated ion channels.

  (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 agreed to share their name with the authors.)

Reviewed by eLife

Fuzzy supertertiary interactions within PSD-95 enable ligand binding

1. George L Hamilton
2. Nabanita Saikia
3. Sujit Basak
4. Franceine S Welcome
5. Fang Wu
6. Jakub Kubiak
7. Changcheng Zhang
8. Yan Hao
9. Claus AM Seidel
10. Feng Ding
11. Hugo Sanabria
12. Mark E Bowen

• Curated by eLife

  Evaluation Summary:

  This paper is of broad interest to investigators studying the function and regulation of protein scaffolds, dynamic protein structure, and the regulation of the postsynaptic density at excitatory synapses. The authors develop an integrated approach using fluorescence-based biochemical methods, disulfide mapping, and discrete molecular dynamic simulations to study the dynamic supertertiary conformation of the synaptic scaffold protein PSD95.

  (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 name with the authors.)

Reviewed by eLife

Interplay of surface interaction and magnetic torque in single-cell motion of magnetotactic bacteria in microfluidic confinement

1. Agnese Codutti
2. Mohammad A Charsooghi
3. Elisa Cerdá-Doñate
4. Hubert M Taïeb
5. Tom Robinson
6. Damien Faivre
7. Stefan Klumpp

• Curated by eLife

  Evaluation Summary:

  The manuscript reports results of a combined experimental and numerical investigation of magnetotactic bacteria in strong spatial confinement and under the influence of an external magnetic field. Single cells are trapped in micrometer-sized microfluidic chambers. A variety of trajectories are found, which depend on the chamber size and the strength of the magnetic field. A detailed understanding of swimming in simple controlled confinement is essential to predict the behavior of motile microorganisms in the complex environments of their natural habitat.

  (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

Control of nuclear size by osmotic forces in Schizosaccharomyces pombe

1. Joël Lemière
2. Paula Real-Calderon
3. Liam J Holt
4. Thomas G Fai
5. Fred Chang

• Curated by eLife

  Evaluation Summary:

  This work offers a simple explanation to a fundamental question in cell biology: what dictates the volume of a cell and of its nucleus, focusing on yeast cells. The central message is that all this can be explained by an osmotic equilibrium, using the classical Van't Hoff's Law. The novelty resides in an effort to provide actual numbers experimentally.

  (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 agreed to share their name with the authors.)

Reviewed by eLife

The Glycan-Specificity of the Pineapple Lectin AcmJRL and its Carbohydrate-Dependent Binding of the SARS-CoV-2 Spike Protein

1. Joscha Meiers
2. Jan Dastbaz
3. Sebastian Adam
4. Sari Rasheed
5. Susanne H. Kirsch
6. Peter Meiser
7. Peter Gross
8. Rolf Müller
9. Alexander Titz

Reviewed by ScreenIT

A coarse-grained NADH redox model enables inference of subcellular metabolic fluxes from fluorescence lifetime imaging

1. Xingbo Yang
2. Gloria Ha
3. Daniel J Needleman

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to scientists who use imaging approaches to study cellular metabolism. It presents a new coarse-grained model for inferring mitochondrial NADH oxidation from NAD(P)H fluorescence lifetime imaging in mouse oocytes. The modeling is thoughtfully and clearly presented, but the validity of some key assumptions of the model and the overall generalizability of the method to other cell types could be strengthened.

  (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 names with the authors.)

Reviewed by eLife

A theory of synaptic transmission

1. Bin Wang
2. Olga K Dudko

• Curated by eLife

  Evaluation Summary:

  The present MS describes an effort to create a general mathematical model of synaptic neurotransmission. The authors invested great efforts to create a complex model of the presynaptic mechanisms. This is an exceptionally challenging task and it falls short of a true general theory. Nonetheless, the model will be an important addition to an emerging field attempting to generate predictive models of complex neuronal biophysical processes, including synaptic transmission.

  (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 basis for substrate selection by the SARS-CoV-2 replicase

1. Brandon F. Malone
2. Jason K. Perry
3. Paul Dominic B. Olinares
4. Hery W. Lee
5. James Chen
6. Todd C. Appleby
7. Joy Y. Feng
8. John P. Bilello
9. Honkit Ng
10. Johanna Sotiris
11. Mark Ebrahim
12. Eugene Y. D. Chua
13. Joshua H. Mendez
14. Ed T. Eng
15. Robert Landick
16. Matthias Götte
17. Brian T. Chait
18. Elizabeth A. Campbell
19. Seth A. Darst

Reviewed by ScreenIT

Revealing druggable cryptic pockets in the Nsp1 of SARS-CoV-2 and other β-coronaviruses by simulations and crystallography

1. Alberto Borsatto
2. Obaeda Akkad
3. Ioannis Galdadas
4. Shumeng Ma
5. Shymaa Damfo
6. Shozeb Haider
7. Frank Kozielski
8. Carolina Estarellas
9. Francesco Luigi Gervasio

• Curated by eLife

  eLife assessment

  SARS-CoV-2 nonstructural protein (Nsp1) has emerged as an attractive target as it plays an important role in modulating the host and viral gene expression. This study describes multiple druggable sites in Nsp1. A 1.1Å co-crystal structure of Nsp1 with a fragment, together with computational studies, provides a framework for the rational design of potential antiviral candidates. This important study is methodologically convincing and will be of interest to researchers in the fields of structural virology and rational drug design.

Reviewed by eLife, ScreenIT