Biophysics

Targeting RNA:protein interactions with an integrative approach leads to the identification of potent YBX1 inhibitors

1. Krystel El Hage
2. Nicolas Babault
3. Olek Maciejak
4. Bénédicte Desforges
5. Pierrick Craveur
6. Emilie Steiner
7. Juan Carlos Rengifo-Gonzalez
8. Hélène Henrie
9. Marie-Jeanne Clement
10. Vandana Joshi
11. Ahmed Bouhss
12. Liya Wang
13. Cyril Bauvais
14. David Pastré

• Curated by eLife

  Evaluation Summary:

  Protein-RNA interactions are involved in many diseases and targeting them with drugs can be valuable. Because protein-RNA complexes are considered difficult to target both computationally and experimentally, an integrated computational-experimental approach to solve this limitation is introduced. The approach is demonstrated by targeting the mRNA-binding protein YB-1, which works remarkably well. Inhibitors in the micromolar range are detected, including a previously approved drug. The main strength here is the proof of concept that protein-RNA interactions are targetable. However, additional data are required to support the central claims of the paper.

  (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

Structure of SARS-CoV-2 M protein in lipid nanodiscs

1. Kimberly A Dolan
2. Mandira Dutta
3. David M Kern
4. Abhay Kotecha
5. Gregory A Voth
6. Stephen G Brohawn

• Curated by eLife

  Evaluation Summary:

  This paper reports the structure of the M protein of SARS-CoV-2, as determined by cryoEM. The structure is well-determined and reveals a homodimer with overall similar structure as ORF3a, another virally encoded protein. The surface charge distribution is skewed towards positive at the C-terminal domain, which suggests roles in interactions with viral N and S proteins, and possibly viral RNA. The work is of relevance to virologists, especially those studying SARS-CoV-2.

  (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, PREreview

Self-organized canals enable long-range directed material transport in bacterial communities

1. Ye Li
2. Shiqi Liu
3. Yingdan Zhang
4. Zi Jing Seng
5. Haoran Xu
6. Liang Yang
7. Yilin Wu

• Curated by eLife

  Evaluation Summary:

  The manuscript describes an interesting phenomenon of long-range transport in self-organized canal structures formed in colonies of the pathogenic bacterium Pseudomonas aeruginosa. The authors measured and analyzed the fluid flows in these open channels, revealing that it is capable of supporting high-speed transport of outer membrane vesicles and bacterial cells over centimeters. This study sheds new light on the potential amplitude of cargo exchange among bacterial communities over long distances.

  (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

Computational model of the full-length TSH receptor

1. Mihaly Mezei
2. Rauf Latif
3. Terry F Davies

• Curated by eLife

  Evaluation Summary:

  This manuscript presents the first molecular dynamics (MD) simulations of full-length membrane-bound Thyroid Stimulating Hormone Receptor (TSHR). The authors find that its linker region (LR) is disordered, contrasting previous models. While this is largely a solid study that would interest researchers working in computational modeling, thyroid hormone metabolism, and signaling, the rationale for the arbitrarily chosen starting model and unclear mechanistic relevance need to be clarified further.

  (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

Rabphilin 3A binds the N-peptide of SNAP-25 to promote SNARE complex assembly in exocytosis

1. Tianzhi Li
2. Qiqi Cheng
3. Shen Wang
4. Cong Ma

• Curated by eLife

  Evaluation Summary:

  Li et al. use biochemical binding analysis to explore the role of Rabphilin 3A in dense-core vesicle exocytosis in neuroendocrine PC12 cells and in an in vitro SNARE assembly assay. They propose that the Rph3A binding to SNAP25 pre-structures the protein to efficiently assemble with Syntaxin and VAMP2, and thus, promoting the vesicle docking and priming process. This work will be of interest to scientists studying the molecular basis of synaptic vesicle release.

  (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

Structure of Geobacter OmcZ filaments suggests extracellular cytochrome polymers evolved independently multiple times

1. Fengbin Wang
2. Chi Ho Chan
3. Victor Suciu
4. Khawla Mustafa
5. Madeline Ammend
6. Dong Si
7. Allon I Hochbaum
8. Edward H Egelman
9. Daniel R Bond

• Curated by eLife

  Evaluation Summary:

  This manuscript reports the CryoEM structure of OmcZ cytochrome nanowires of Geobacter sulfurreducens, the third cytochrome nanowire of Geobacter to be structurally resolved. OmcZ differs structurally from these previously determined nanowire structures, showing a different heme chain configuration. Based on these and other differences the authors speculate about the evolutionary origin of these nanowires and the mechanism of long-range electron transport. This manuscript is an important contribution to the field of electron transfer and will be of interest to everyone working in electron transfer and filament formation and interested in their 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 #1 agreed to share their name with the authors.)

Reviewed by eLife

Membrane curvature governs the distribution of Piezo1 in live cells

1. Shilong Yang
2. Xinwen Miao
3. Steven Arnold
4. Boxuan Li
5. Alan T. Ly
6. Huan Wang
7. Matthew Wang
8. Xiangfu Guo
9. Medha M. Pathak
10. Wenting Zhao
11. Charles D. Cox
12. Zheng Shi

• Curated by Biophysics Colab

  Endorsement statement (6 December 2022)

  The preprint by Yang et al. asks how the shape of the membrane influences the localization of mechanosensitive Piezo channels. The authors use a creative approach involving methods that distort the plasma membrane by generating blebs and artificial filopodia. They convincingly show that curvature of the lipid environment influences Piezo1 localization, such that increased curvature causes channel depletion, and that application of the chemical modulator Yoda1 is sufficient to allow channels to enter filopodia. The study provides support for a provocative “flattening model” of Yoda1 action, and should inspire future studies by researchers interested in mechanosensitive channels and membrane curvature.

  (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 Biophysics Colab

Architecture of the chikungunya virus replication organelle

1. Timothée Laurent
2. Pravin Kumar
3. Susanne Liese
4. Farnaz Zare
5. Mattias Jonasson
6. Andreas Carlson
7. Lars-Anders Carlson

Reviewed by Review Commons

Ranking Peptide Binders by Affinity with AlphaFold**

1. Liwei Chang
2. Alberto Perez

Reviewed by Arcadia Science

Versatile patterns in the actin cortex of motile cells: Self-organized pulses can coexist with macropinocytic ring-shaped waves

1. Arik Yochelis
2. Sven Flemming
3. Carsten Beta

• Curated by eLife

  Evaluation Summary:

  Individual cells may act in response to stimuli or in a self-organized fashion. The relative weight of these two modes determines in the end to which degree cells or rather organs/organisms carry function. This study reports an example of very complex self-organization of actin waves as the coexistence of slowly moving broad waves of high F-actin concentration and rapidly propagating planar F-actin pulses. The paper is interesting for everybody interested in conceptual questions like signalling versus self-organization, in cellular morpho-dynamics and theory of dynamic patterns.

  (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