Biochemistry

Colloidal Aggregators in Biochemical SARS-CoV-2 Repurposing Screens

1. Henry R. O’Donnell
2. Tia A. Tummino
3. Conner Bardine
4. Charles S. Craik
5. Brian K. Shoichet

Reviewed by ScreenIT

Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays

1. Chunlong Ma
2. Haozhou Tan
3. Juliana Choza
4. Yuyin Wang
5. Jun Wang

Reviewed by ScreenIT

Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice

1. Zdravka Daneva
2. Matteo Ottolini
3. Yen Lin Chen
4. Eliska Klimentova
5. Maniselvan Kuppusamy
6. Soham A Shah
7. Richard D Minshall
8. Cheikh I Seye
9. Victor E Laubach
10. Brant E Isakson
11. Swapnil K Sonkusare

• Curated by eLife

  Evaluation Summary:

  This study, which makes a connection between several proteins known to regulate endothelial function in pulmonary arteries, may be of interest to vascular, pulmonary and ion channel physiologists. The study provides compelling evidence that ATP released from pulmonary artery endothelial cell (EC) pannexin1 channels activates TRPV4 channels via an EC P2Y2R-PLC-DAG-PKC alpha pathway that is facilitated by the scaffolding protein Caveolin-1 and that this pathway helps to maintain low pulmonary vascular resistance and pulmonary artery pressure. Identification of this pathway provides new drug targets to improve pulmonary endothelial function in disease states such characterized by impaired endothelial function. What remains to be established or understood is the physiological stimulus for activation of the pannexin1 channels and ATP release and also the potential dark-side of overactivity of EC TRPV4 channels, which appear to have negative effects on EC function.

  (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

Structural remodeling of SARS-CoV-2 spike protein glycans reveals the regulatory roles in receptor-binding affinity

1. Yen-Pang Hsu
2. Martin Frank
3. Debopreeti Mukherjee
4. Vladimir Shchurik
5. Alexey Makarov
6. Benjamin F Mann

Reviewed by ScreenIT

Structural analysis of receptor binding domain mutations in SARS-CoV-2 variants of concern that modulate ACE2 and antibody binding

1. Dhiraj Mannar
2. James W. Saville
3. Xing Zhu
4. Shanti S. Srivastava
5. Alison M. Berezuk
6. Steven Zhou
7. Katharine S. Tuttle
8. Andrew Kim
9. Wei Li
10. Dimiter S. Dimitrov
11. Sriram Subramaniam

Reviewed by ScreenIT

Antiviral cyclic peptides targeting the main protease of SARS-CoV-2

1. Jason Johansen-Leete
2. Sven Ullrich
3. Sarah E. Fry
4. Rebecca Frkic
5. Max J. Bedding
6. Anupriya Aggarwal
7. Anneliese S. Ashhurst
8. Kasuni B. Ekanayake
9. Mithun C. Mahawaththa
10. Vishnu M. Sasi
11. Stephanie Luedtke
12. Daniel J. Ford
13. Anthony J. O'Donoghue
14. Toby Passioura
15. Mark Larance
16. Gottfried Otting
17. Stuart Turville
18. Colin J. Jackson
19. Christoph Nitsche
20. Richard J. Payne

Reviewed by ScreenIT

A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation

1. Gajanan S Patil
2. Priyadarshan Kinatukara
3. Sudipta Mondal
4. Sakshi Shambhavi
5. Ketan D Patel
6. Surabhi Pramanik
7. Noopur Dubey
8. Subhash Narasimhan
9. Murali Krishna Madduri
10. Biswajit Pal
11. Rajesh S Gokhale
12. Rajan Sankaranarayanan

• Curated by eLife

  Evaluation Summary:

  This study addresses the structural basis of the ability of fatty acyl-AMP ligases (FAAL) to exclude condensation of activated fatty acids with coenzyme-A and facilitate the reaction with other 4-phosphopantetheine linked acceptors. This issue is of significant interest with regard to understanding how certain fatty acids are channeled to specific metabolic fates. The structural question at hand is the apparent discrimination of the CoA moiety (adenosine 3',5'-bisphosphate) versus a holo-ACP tethered to the 4-phosphopantethein head group. This work will contribute significantly to our current knowledge of how distinct classes of enzymes divert fatty acids to virulent lipids in mycobacteria, and it will be more broadly of interest for metabolic engineering.

  (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

Secondary metabolites of Hülle cells mediate protection of fungal reproductive and overwintering structures against fungivorous animals

1. Li Liu
2. Christoph Sasse
3. Benedict Dirnberger
4. Oliver Valerius
5. Enikő Fekete-Szücs
6. Rebekka Harting
7. Daniela E Nordzieke
8. Stefanie Pöggeler
9. Petr Karlovsky
10. Jennifer Gerke
11. Gerhard H Braus

• Curated by eLife

  Evaluation Summary:

  Hülle cells, a type of cells formed by fungal species of the genus Aspergillus, are specialized cells that surround the sexual fruiting bodies of ascomycete fungi and are thought to nurse the fruiting bodies during fungal development. In this work, Liu et al. suggest that these cells have a strong ecological impact because they contain specific secondary metabolites that help the fungus to "withstand" the attack by fungivorous animals, like springtails, and also inhibit sexual reproduction of other fungi. This work will likely have a major impact on our view on the development and ecology of fungi as well as on the ecological functions of secondary metabolites.

  (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 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling

1. Jugal Mohapatra
2. Kyuto Tashiro
3. Ryan L Beckner
4. Jorge Sierra
5. Jessica A Kilgore
6. Noelle S Williams
7. Glen Liszczak

• Curated by eLife

  Evaluation Summary:

  Poly-ADP-ribosylation (poly-ADPr) is a major histone modification that plays critical roles in DNA damage. However careful mechanistic dissection of the role of poly-ADPr has been challenging as the modification is found on multiple proteins and there is heterogeneity in terms of poly-ADP-ribosylation chain length and amino acid location of attachment. The PARP1-dependent semi-synthetic strategy developed by the authors allows generation of nucleosomes with mono ADP ribose and defined lengths of poly-ADPr chains at specific histone serine residues. The utility of this method is clearly demonstrated by the authors' findings that ALC1, a chromatin remodeler that recognizes poly-ADPr is stimulated substantially by the presence of poly-ADPr on H2A and H3.

  (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

Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant

1. Jun Zhang
2. Tianshu Xiao
3. Yongfei Cai
4. Christy L. Lavine
5. Hanqin Peng
6. Haisun Zhu
7. Krishna Anand
8. Pei Tong
9. Avneesh Gautam
10. Megan L. Mayer
11. Richard M. Walsh
12. Sophia Rits-Volloch
13. Duane R. Wesemann
14. Wei Yang
15. Michael S. Seaman
16. Jianming Lu
17. Bing Chen

Reviewed by ScreenIT