Biophysics

Dynamic allostery in substrate binding by human thymidylate synthase

1. Jeffrey P Bonin
2. Paul J Sapienza
3. Andrew L Lee

• Curated by eLife

  Evaluation Summary:

  The authors analyze the mechanisms of entropically driven cooperativity in the human thymidylate synthase (hTS), an enzyme essential for DNA replication and a promising target for anticancer drugs. The authors conclude that the cooperative binding of dUMP ligands to its two identical sites arises from a disproportionate reduction in the enzyme's conformational entropy upon binding the first ligand. The results provide rare insights into the mechanisms of ligand binding for an essential human protein and should be of great interest to readers interested in enzyme structure/dynamics/function relationships, cooperativity and allostery, and possible drug targeting of thymidylate synthase.

  (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

Threonine phosphorylation regulates the molecular assembly and signaling of EGFR in cooperation with membrane lipids

1. Ryo Maeda
2. Hiroko Tamagaki-Asahina
3. Takeshi Sato
4. Masataka Yanagawa
5. Yasushi Sako

Reviewed by Review Commons

Structures of topoisomerase V in complex with DNA reveal unusual DNA-binding mode and novel relaxation mechanism

1. Amy Osterman
2. Alfonso Mondragón

• Curated by eLife

  Evaluation Summary:

  Osterman and Modragon report the first crystal structure of topoisomerase V in complex with DNA. Topoisomerase V is an unusual protein in that homologs have only been found in the archaeal Methanopyrus genus. The paper is likely of interest to those studying topoisomerase biology and biochemistry, and the wider audience interested in DNA replication and repair transactions.

  (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

Calcineurin-fusion facilitates cryo-EM structure determination of a Family A GPCR

1. Jun Xu
2. Geng Chen
3. Haoqing Wang
4. Sheng Cao
5. Jie Heng
6. Xavier Deupi
7. Yang Du
8. Brian K. Kobilka

Reviewed by Biophysics Colab

Evolutionary divergence of anaphase spindle mechanics in nematode embryos constrained by antagonistic pulling and viscous forces

1. Dhruv Khatri
2. Thibault Brugière
3. Chaitanya A. Athale
4. Marie Delattre

• Curated by eLife

  Evaluation Summary:

  This work will be of interest to cell biologists studying the mechanism of asymmetric cell division and its diversity across species. Building on their earlier work, the authors show that that there is considerable variability in the mechanics of the spindle among six nematode species studied here. While the authors' main conclusion is plausible - that spindle oscillations require high force and low viscosity - stronger support by the data would be needed.

  (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

Conformational fingerprinting of allosteric modulators in metabotropic glutamate receptor 2

1. Brandon Wey-Hung Liauw
2. Arash Foroutan
3. Michael R Schamber
4. Weifeng Lu
5. Hamid Samareh Afsari
6. Reza Vafabakhsh

• Curated by eLife

  Evaluation Summary:

  The authors advance our understanding of the molecular underpinnings of allostery in GPCRs by showing the effects of allosteric modulators of mGluR2 on receptor conformation at distinct sites in the presence and absence of orthosteric modulators. This is important as drugs and drug candidates acting outside the site where the orthosteric or endogenous ligands bind are harder to identify. This work provides insights into allosteric changes at the level of individual receptors and provides a new path for drug discovery and is this of interest to colleagues studying GPCRs in health and disease.

  (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

The Candida albicans virulence factor candidalysin polymerizes in solution to form membrane pores and damage epithelial cells

1. Charles M Russell
2. Katherine G Schaefer
3. Andrew Dixson
4. Amber LH Gray
5. Robert J Pyron
6. Daiane S Alves
7. Nicholas Moore
8. Elizabeth A Conley
9. Ryan J Schuck
10. Tommi A White
11. Thanh D Do
12. Gavin M King
13. Francisco N Barrera

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest to several fields, in particular to microbiologists and structural biologists interested in pore-forming proteins and peptides. The data presented reveal insights into the mode of action of a newly identified peptide toxin secreted by Candida albicans (candidalysin). Using different techniques the authors propose and test a model for membrane perforation by candidalysin and identify an intriguing inactive mutant. While the presented data supports the main conclusions of the paper some of the initial assumptions need further assessment while the described mutants could benefit from more extensive characterization.

  (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

Effective mechanical potential of cell–cell interaction explains three-dimensional morphologies during early embryogenesis

1. Hiroshi Koyama
2. Hisashi Okumura
3. Atsushi M. Ito
4. Kazuyuki Nakamura
5. Tetsuhisa Otani
6. Kagayaki Kato
7. Toshihiko Fujimori

• Curated by eLife

  Evaluation Summary:

  In this manuscript, effective force-distance curves between cells are inferred for various tissues. This study is potentially interesting for researchers interested in tissue dynamics, because computer models of growing cellular tissues are becoming an increasingly important tool to understand experimental data and eventually predict medical interventions.

  (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 motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels

1. Bochuan Teng
2. Joshua P Kaplan
3. Ziyu Liang
4. Zachary Krieger
5. Yu-Hsiang Tu
6. Batuujin Burendei
7. Andrew B Ward
8. Emily R Liman

• Curated by eLife

  Evaluation Summary:

  The manuscript shows that OTOP proton channels are proton-gated with distinct pH sensitivities, and identifies regions on the proteins that alter pH-dependent gating. The main claims are well supported by the data. These findings are likely to be of interest to researchers studying acid/base physiology, sensory physiology, or ion channel biophysics.

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

Reviewed by eLife

Proton-transporting heliorhodopsins from marine giant viruses

1. Shoko Hososhima
2. Ritsu Mizutori
3. Rei Abe-Yoshizumi
4. Andrey Rozenberg
5. Shunta Shigemura
6. Alina Pushkarev
7. Masae Konno
8. Kota Katayama
9. Keiichi Inoue
10. Satoshi P Tsunoda
11. Oded Béjà
12. Hideki Kandori

• Curated by eLife

  Evaluation Summary:

  Hososhima et al. characterize a marine virus Heliorhodopsin as the first of its class to show ion transport activity. These bacteriorhodopsin homologs have been recently described and the present careful characterization of V2HeR3 represents an important step in the understanding of these interesting membrane proteins. Though the experiments are carried out carefully and the results, in general, support the conclusions, some experiments are needed and the interpretation of results needs to be clarified.

  (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