Molecular Biology

Disrupting ACE2 Dimerization Mitigates the Infection by SARS-COV-2

1. Jiaqi Zhu
2. Yue Su
3. Young Tang

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Biphasic regulation of osteoblast development via the ERK MAPK–mTOR pathway

1. Jung-Min Kim
2. Yeon-Suk Yang
3. Jaehyoung Hong
4. Sachin Chaugule
5. Hyonho Chun
6. Marjolein CH van der Meulen
7. Ren Xu
8. Matthew B Greenblatt
9. Jae-hyuck Shim

• Curated by eLife

  Evaluation Summary:

  This work provides a novel insight into regulation of osteogenesis by ERK-mTOR pathway. The authors proposed that the effect of Erk pathway would be mediated mTOR2-SGK1. The mitochondrial metabolisms appears to be involved in this regulation. This study is well performed, and the manuscript is clearly written.

  (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

A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation

1. Morgane Boone
2. Lan Wang
3. Rosalie E Lawrence
4. Adam Frost
5. Peter Walter
6. Michael Schoof

• Curated by eLife

  Evaluation Summary:

  This manuscript addresses a significant and timely topic in translational control and will be of interest to researchers studying molecular biology or diseases impacted by the Integrated Stress Response (ISR). The combination of biochemical, structural, and in-cell experiments constitutes a comprehensive study that supports the proposed model for allosteric regulation of the active/inactive states of the eIF2B complex. The findings are relevant to neuropathologies, infectious and inflammatory diseases, diabetes, and metabolic disorders.

  (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

MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation

1. Rafael Romero-Becerra
2. Alfonso Mora
3. Elisa Manieri
4. Ivana Nikolic
5. Ayelén Melina Santamans
6. Valle Montalvo-Romeral
7. Francisco Miguel Cruz
8. Elena Rodríguez
9. Marta León
10. Luis Leiva-Vega
11. Laura Sanz
12. Víctor Bondía
13. David Filgueiras-Rama
14. Luis Jesús Jiménez-Borreguero
15. José Jalife
16. Barbara Gonzalez-Teran
17. Guadalupe Sabio

• Curated by eLife

  Evaluation Summary:

  This paper demonstrates that deletion of MKK6 reduces life span in mice, and leads to cardiac hypertrophy that progresses to cardiac dilatation and fibrosis with age. The authors also demonstrate that the mechanism for this phenomenon is through reduced p38a activation while causing MKK3-p38g/d hyperphosphorylation and increased mTOR signaling. The authors extend previous studies (that demonstrate a role for P38 proteins as downstream effector of MKK6) and identify the isoform of P38 that plays a role in this process. Overall, the studies in this paper are conducted carefully and most of the conclusions are based on the reported data.

  (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

An Ultralong Bovine CDRH3 that Targets a Conserved, Cryptic Epitope on SARS-CoV and SARS-CoV-2

1. Matthew J. Burke
2. James N.F. Scott
3. Thomas Minshull
4. Peter G. Stockley
5. Antonio N. Calabrese
6. Joan Boyes

Reviewed by ScreenIT

Convergence of immune escape strategies highlights plasticity of SARS-CoV-2 spike

1. Xiaodi Yu
2. Jarek Juraszek
3. Lucy Rutten
4. Mark J. G. Bakkers
5. Sven Blokland
6. Jelle M. Melchers
7. Niels J. F. van den Broek
8. Annemiek Y. W. Verwilligen
9. Pravien Abeywickrema
10. Johan Vingerhoets
11. Jean-Marc Neefs
12. Shah A. Mohamed Bakhash
13. Pavitra Roychoudhury
14. Alex Greninger
15. Sujata Sharma
16. Johannes P. M. Langedijk

Reviewed by ScreenIT

Identification of C270 as a novel site for allosteric modulators of SARS-CoV-2 papain-like protease

1. Hangchen Hu
2. Qian Wang
3. Haixia Su
4. Qiang Shao
5. Wenfeng Zhao
6. Guofeng Chen
7. Minjun Li
8. Yechun Xu

Reviewed by ScreenIT

Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules

1. Yuzuru Itoh
2. Vivek Singh
3. Anas Khawaja
4. Andreas Naschberger
5. Minh Duc Nguyen
6. Joanna Rorbach
7. Alexey Amunts

• Curated by eLife

  Evaluation Summary:

  As a consequence of the bacterial origin of mitochondria, a range of medically relevant antimicrobials can affect not only bacteria but also human cells. For example, they may inhibit mitochondrial protein synthesis, giving rise to important side-effects during medical treatment, such as hearing loss or renal toxicity in patients treated with aminoglycosides. In this manuscript, the authors present the structure of the human mitochondrial small ribosomal subunit bound to one such antibiotics, streptomycin. This cryoEM-based structural analysis will be of interest to scientists in the infectious disease community as well as those interested in ribosome structural biology. It provides an important advance that could aid future medicinal chemistry efforts to improve the therapeutic potential of streptomycin derivatives.

  (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

The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate

1. Minato Hirano
2. Gaddiel Galarza-Muñoz
3. Chloe Nagasawa
4. Geraldine Schott
5. Liuyang Wang
6. Alejandro L Antonia
7. Vaibhav Jain
8. Xiaoying Yu
9. Steven G Widen
10. Farren BS Briggs
11. Simon G Gregory
12. Dennis C Ko
13. William S Fagg
14. Shelton Bradrick
15. Mariano A Garcia-Blanco

• Curated by eLife

  Evaluation Summary:

  In this study, DDX39B, a factor with known functions in mRNA splicing and nuclear export, is shown to regulate Foxp3, a lineage marker for T-regulatory cells in the immune system. The interactions are positioned in the context of multiple sclerosis and autoimmune inflammatory condition. The work would be of interest to immunologists and those studying RNA-mediated regulation and cellular 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Topologically engineered antibodies and Fc-fusion proteins: a new class of multifunctional therapeutic candidates for SARS-CoV-2, cancer, and other disease

1. Daniel J. Capon
2. Larisa Troitskaya
3. Nelson Lap Shun Chan
4. Marina Fomin
5. Ursula Edman
6. Brendon Frank
7. Jing Jin
8. Rachel Martinelli
9. Benjamin Z. Capon
10. Ginger A. Ferguson
11. Malcolm L. Gefter
12. Graham Simmons

Reviewed by ScreenIT