Biochemistry

Variable inhibition of unwinding rates of DNA catalyzed by the SARS-Cov-2 (COV19) helicase nsp13 by structurally distinct single DNA lesions

1. A.H. Sales
2. S. Ciervo
3. T. Lupoli
4. V. Shafirovich
5. N.E. Geacintov

Reviewed by ScreenIT

Branched ubiquitin chain binding and deubiquitination by UCH37 facilitate proteasome clearance of stress-induced inclusions

1. Aixin Song
2. Zachary Hazlett
3. Dulith Abeykoon
4. Jeremy Dortch
5. Andrew Dillon
6. Justin Curtiss
7. Sarah Bollinger Martinez
8. Christopher P Hill
9. Clinton Yu
10. Lan Huang
11. David Fushman
12. Robert E Cohen
13. Tingting Yao

• Curated by eLife

  Evaluation Summary:

  This manuscript addresses the role of the deubiquitylating enzyme UCH37 in facilitating proteasomal clearance of branched polyubiquitylated substrates. Using a wide-range of chemical biological, biophysical and cell biological techniques, the authors have convincingly demonstrated that UCH37 binds to branched ubiquitin trimers, with at least one K48 linkage, by binding to both distal ubiquitins attached to the proximal, or central, ubiquitin. They further demonstrate that mutations of UCH37 lead to the formation of proteasomal foci in cells and that these foci are rich in polyubiquitinated species, presumably due to the lack of debranching by UCH37. Overall, this excellent study adds to our understanding of UCH37 function, especially with regard to the newly observed phenomenon of reversible proteasome aggregation in cells. Readers will benefit from the large array of ubiquitin-centric tools that are described to study key aspects of UCH37 function and from knowledge of the specific role of UCH37.

  (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 and ion-release mechanism of PIB-4-type ATPases

1. Christina Grønberg
2. Qiaoxia Hu
3. Dhani Ram Mahato
4. Elena Longhin
5. Nina Salustros
6. Annette Duelli
7. Pin Lyu
8. Viktoria Bågenholm
9. Jonas Eriksson
10. Komal Umashankar Rao
11. Domhnall Iain Henderson
12. Gabriele Meloni
13. Magnus Andersson
14. Tristan Croll
15. Gabriela Godaly
16. Kaituo Wang
17. Pontus Gourdon

• Curated by eLife

  Evaluation Summary:

  This paper presents crystal structures of sCoaT, a heavy metal transporting P-type ATPase. These structures and complementary functional data define the overall fold of this protein and provide insight into several mechanistic features, including a conserved histidine proposed to act as a novel counter-ion during transport. The study will be of interest to biochemists and microbiologists interested in the transport of transition metals, structural biology of membrane proteins and drug 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 #1 agreed to share their name with the authors.)

Reviewed by eLife

High-Throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain

1. Morgan Dasovich
2. Junlin Zhuo
3. Jack A. Goodman
4. Ajit Thomas
5. Robert Lyle McPherson
6. Aravinth Kumar Jayabalan
7. Veronica F. Busa
8. Shang-Jung Cheng
9. Brennan A. Murphy
10. Karli R. Redinger
11. Yousef M. O. Alhammad
12. Anthony R. Fehr
13. Takashi Tsukamoto
14. Barbara S. Slusher
15. Jürgen Bosch
16. Huijun Wei
17. Anthony K. L. Leung

Reviewed by ScreenIT

Structural insights into recognition of chemokine receptors by Staphylococcus aureus leukotoxins

1. Paul Lambey
2. Omolade Otun
3. Xiaojing Cong
4. François Hoh
5. Luc Brunel
6. Pascal Verdié
7. Claire M Grison
8. Fanny Peysson
9. Sylvain Jeannot
10. Thierry Durroux
11. Cherine Bechara
12. Sébastien Granier
13. Cédric Leyrat

• Curated by eLife

  Evaluation Summary:

  This manuscript reports on the interaction of LukE toxin with chemokine receptors. The study is extensive and employs a wide array of tools, although further experimentation would be needed to substantiate the inferences made by the authors. The paper will be of interest to scientists interested in host-pathogen interactions as it delves into understanding the molecular mechanism and interactions of an important toxin interacting with cellular receptors.

  (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

Metabolic Snapshot of Plasma Samples Reveals New Pathways Implicated in SARS-CoV-2 Pathogenesis

1. Oihane E. Albóniga
2. Daniel Jiménez
3. Matilde Sánchez-Conde
4. Pilar Vizcarra
5. Raquel Ron
6. Sabina Herrera
7. Javier Martínez-Sanz
8. Elena Moreno
9. Santiago Moreno
10. Coral Barbas
11. Sergio Serrano-Villar

Reviewed by ScreenIT

Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation

1. Dorota Rousová
2. Vaishnavi Nivsarkar
3. Veronika Altmannova
4. Vivek B Raina
5. Saskia K Funk
6. David Liedtke
7. Petra Janning
8. Franziska Müller
9. Heidi Reichle
10. Gerben Vader
11. John R Weir

• Curated by eLife

  Evaluation Summary:

  Using a combination of biochemical approaches and yeast genetics, the authors study the function of the DNA double-strand break factor Mer2. The authors show that Mer2 interacts with a meiotic chromosome axis factor (Hop1), nucleosomes, the nucleosome-binding protein Spp1, and the double-strand break factor Mre11 to serve as a "keystone" for meiotic DNA break formation. These findings represent an important step forward in understanding the functions of this highly conserved protein in meiosis.

  (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

LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein

1. Jarrod Shilts
2. Thomas W. M. Crozier
3. Ana Teixeira-Silva
4. Ildar Gabaev
5. Pehuén Pereyra Gerber
6. Edward J. D. Greenwood
7. Samuel James Watson
8. Brian M. Ortmann
9. Christian M. Gawden-Bone
10. Tekle Pauzaite
11. Markus Hoffmann
12. James A. Nathan
13. Stefan Pöhlmann
14. Nicholas J. Matheson
15. Paul J. Lehner
16. Gavin J. Wright

Reviewed by ScreenIT

Transcription initiation at a consensus bacterial promoter proceeds via a ‘bind-unwind-load-and-lock’ mechanism

1. Abhishek Mazumder
2. Richard H Ebright
3. Achillefs N Kapanidis

• Curated by eLife

  Evaluation Summary:

  This work aims to provide insight into the molecular mechanism by which RNA polymerase separates the two strands of DNA, generating a single-stranded template for RNA synthesis. Using single-molecule analysis, the authors examined two conformational transitions taking place during RNA transcription initiation: DNA unwinding and RNAP clamp movements. Pending addition of some important controls, the paper will help to distinguish between two competing hypotheses within the literature. The work will be of relevance to a wide range of researchers interested in the molecular basis of gene expression and gene regulation.

  (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

Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19

1. Malgorzata Wygrecka
2. Anna Birnhuber
3. Benjamin Seeliger
4. Laura Michalick
5. Oleg Pak
6. Astrid-Solveig Schultz
7. Fabian Schramm
8. Martin Zacharias
9. Gregor Gorkiewicz
10. Sascha David
11. Tobias Welte
12. Julius J. Schmidt
13. Norbert Weissmann
14. Ralph T. Schermuly
15. Guillermo Barreto
16. Liliana Schaefer
17. Philipp Markart
18. Markus C. Brack
19. Stefan Hippenstiel
20. Florian Kurth
21. Leif E. Sander
22. Martin Witzenrath
23. Wolfgang M. Kuebler
24. Grazyna Kwapiszewska
25. Klaus T. Preissner

Reviewed by ScreenIT