Biophysics

Probing the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility

1. Zhongwen Chen
2. Dongmyung Oh
3. Kabir Hassan Biswas
4. Ronen Zaidel-Bar
5. Jay T Groves

• Curated by eLife

  Evaluation Summary:

  These data provide in vivo evidence for a previously described kinetic-proofreading mechanism in phase-separated condensates. The strength is being able to compare the impacts of clustering of signaling molecules with a non-clustered control in the same cell. The limitations are that there is not necessarily new biological insight gained and the effects reported are surprisingly modest compared with expectations from reconstituted systems. This paper will be of broad interest to scientists who study membrane-associated cell signaling.

  (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

Allosteric communication in DNA polymerase clamp loaders relies on a critical hydrogen-bonded junction

1. Subu Subramanian
2. Kent Gorday
3. Kendra Marcus
4. Matthew R Orellana
5. Peter Ren
6. Xiao Ran Luo
7. Michael E O'Donnell
8. John Kuriyan

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest not only to scientists working in the primary field of DNA replication, but also to molecular biologists employing deep mutagenesis as well as structural biologists interested in the functions of the broader class of AAA+ ATPase molecular machines. The work examines relationships between protein sequence, structure and function in the bacteriophage T4 clamp-clamp loader complex, a highly studied AAA+ ATPase that deposits ring-shaped proteins onto DNA to support DNA polymerase processivity and DNA replication. The clamp loader system is revealed to have a high tolerance to amino acid substitution, with little correlation between permitted substitutions and phylogenetic variation. A hitherto unrecognized residue in the clamp loader, which appears to be shared among certain AAA+ ATPase members, is identified as critical for the maintenance of a functional structure and for allosteric coupling. The key claims of the paper are well supported by the data presented, and the employed methodology has undergone rigorous validation. Although a few control studies are still needed, this is a novel and significant paper overall.

  (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

Structural Basis for Allosteric Control of the SERCA-Phospholamban Membrane Complex by Ca ²⁺ and cAMP-dependent Phosphorylation

1. Daniel K. Weber
2. Máximo Sanz-Hernández
3. U. Venkateswara Reddy
4. Songlin Wang
5. Erik K. Larsen
6. Tata Gopinath
7. Martin Gustavsson
8. Razvan L. Cornea
9. David D. Thomas
10. Alfonso De Simone
11. Gianluigi Veglia

• Curated by eLife

  Evaluation Summary:

  There are many of membrane-embedded mini-proteins, which fulfill a large range of regulatory functions. One of them is phospholamban, a single transmembrane helix protein that regulates the sarcoplasmic reticulum Ca2+-ATPase by binding in the membrane. The work presented here combines new experiments with computer simulations with the aim of arriving at a more definitive answer to the long-standing mechanistic question of how exactly phosphorylation of phospholamban modulates its regulatory behavior. In this manuscript, an allosteric mechanism is presented, which could be of general importance for the whole family of these mini-proteins.

  (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

A Brownian ratchet model for DNA loop extrusion by the cohesin complex

1. Torahiko L Higashi
2. Georgii Pobegalov
3. Minzhe Tang
4. Maxim I Molodtsov
5. Frank Uhlmann

• Curated by eLife

  Evaluation Summary:

  This work combines experiments and simulations together with previously reported biophysical and structural observations to develop a structure-based model that provides mechanistic insight into the two functions of cohesin: cohesion and loop extrusion. This intriguing and informative manuscript will be of broad interest to those working in the fields of chromatin structure, chromosome biology and molecular machines. While the data and analysis support the authors' conclusions, the presentation of the work can be improved for clarity.

  (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

SSNA1 stabilizes dynamic microtubules and detects microtubule damage

1. Elizabeth J Lawrence
2. Goker Arpag
3. Cayetana Arnaiz
4. Marija Zanic

• Curated by eLife

  Evaluation Summary:

  In this manuscript, Lawrence et al. investigate the direct effects of the microtubule-associated protein, SSNA1, on microtubule dynamics and damage using purified proteins and TIRF microscopy. The authors conclude that SSNA1 is a microtubule stabilizing protein and a sensor of microtubule damage. This paper is of high interest to scientists within the field of microtubule mechanics and of broad interest to scientists studying cilia, cell division and neuronal development.

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

Reviewed by eLife

Extracellular Vimentin as a Target Against SARS‐CoV‐2 Host Cell Invasion

1. Łukasz Suprewicz
2. Maxx Swoger
3. Sarthak Gupta
4. Ewelina Piktel
5. Fitzroy J. Byfield
6. Daniel V. Iwamoto
7. Danielle Germann
8. Joanna Reszeć
9. Natalia Marcińczyk
10. Robert J. Carroll
11. Paul A. Janmey
12. J. M. Schwarz
13. Robert Bucki
14. Alison E. Patteson

Reviewed by Rapid Reviews Infectious Diseases, PREreview, ScreenIT

Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics

1. Ioannis Galdadas
2. Shen Qu
3. Ana Sofia F Oliveira
4. Edgar Olehnovics
5. Andrew R Mack
6. Maria F Mojica
7. Pratul K Agarwal
8. Catherine L Tooke
9. Francesco Luigi Gervasio
10. James Spencer
11. Robert A Bonomo
12. Adrian J Mulholland
13. Shozeb Haider

• Curated by eLife

  Evaluation Summary:

  This manuscript presents a computational study aiming to understand the allosteric signaling propagation pathway in two class-A beta-lactamases. The results of this study will be of interest to the readers in the fields of beta-lactamase, antibiotic resistance, and enzyme allostery.

  (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. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

StormGraph: A graph-based algorithm for quantitative clustering analysis of diverse single-molecule localization microscopy data

1. Joshua M. Scurll
2. Libin Abraham
3. Da Wei Zheng
4. Reza Tafteh
5. Keng C. Chou
6. Michael R. Gold
7. Daniel Coombs

Reviewed by eLife

Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing

1. Jesse R Holt
2. Wei-Zheng Zeng
3. Elizabeth L Evans
4. Seung-Hyun Woo
5. Shang Ma
6. Hamid Abuwarda
7. Meaghan Loud
8. Ardem Patapoutian
9. Medha M Pathak

• Curated by eLife

  Evaluation Summary:

  The manuscript links a critical physiological function of the skin, wound healing to the ability of skin cells to migrate and the modification of migration by the mechanosensitive ion channel Piezo1. The topic of the manuscript is timely, relevant and would be of interest to a broad audience. The experimental design followed by the authors is straightforward and elegant, and the majority of the conclusions are well supported by the results.

  (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

Cryo-EM structure of the yeast TREX complex and coordination with the SR-like protein Gbp2

1. Yihu Xie
2. Bradley P Clarke
3. Yong Joon Kim
4. Austin L Ivey
5. Pate S Hill
6. Yi Shi
7. Yi Ren

• Curated by eLife

  Evaluation Summary:

  This is an interesting paper describing the structure of the yeast THO:Sub2 complex and how it interacts with the SR like protein Gbp2. The paper extends what we have learned from two recently published Tho:Sub2 complex structures by the Conti and Plaschka groups in two ways. Firstly, it shows how Gbp2 interacts with the THO complex. Secondly, it reveals a substantially different orientation between THO:Sub2 protomers compared with the earlier structure, so provides more information on the flexibility and range of movements that the two protomers might make with respect to each other. The structural inferences are supported by some biochemical experiments but mechanistically the work has limitations, similar to other recent cryo-EM structures of this complex. However, this is an important structure of wide interest to people working on gene expression in eukaryotes and it undoubtedly advances the field.

  (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 opted to remain anonymous to the authors.)

Reviewed by eLife