Biochemistry

Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease

1. Vasundara Srinivasan
2. Hévila Brognaro
3. Prince R. Prabhu
4. Edmarcia Elisa de Souza
5. Sebastian Günther
6. Patrick Y. A. Reinke
7. Thomas J. Lane
8. Helen Ginn
9. Huijong Han
10. Wiebke Ewert
11. Janina Sprenger
12. Faisal H. M. Koua
13. Sven Falke
14. Nadine Werner
15. Hina Andaleeb
16. Najeeb Ullah
17. Bruno Alves Franca
18. Mengying Wang
19. Angélica Luana C. Barra
20. Markus Perbandt
21. Martin Schwinzer
22. Christina Schmidt
23. Lea Brings
24. Kristina Lorenzen
25. Robin Schubert
26. Rafael Rahal Guaragna Machado
27. Erika Donizette Candido
28. Danielle Bruna Leal Oliveira
29. Edison Luiz Durigon
30. Stephan Niebling
31. Angelica Struve Garcia
32. Oleksandr Yefanov
33. Julia Lieske
34. Luca Gelisio
35. Martin Domaracky
36. Philipp Middendorf
37. Michael Groessler
38. Fabian Trost
39. Marina Galchenkova
40. Aida Rahmani Mashhour
41. Sofiane Saouane
42. Johanna Hakanpää
43. Markus Wolf
44. Maria Garcia Alai
45. Dusan Turk
46. Arwen R. Pearson
47. Henry N. Chapman
48. Winfried Hinrichs
49. Carsten Wrenger
50. Alke Meents
51. Christian Betzel

Reviewed by ScreenIT

A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor

1. Yongjian Huang
2. Jana Ognjenovic
3. Deepti Karandur
4. Kate Miller
5. Alan Merk
6. Sriram Subramaniam
7. John Kuriyan

• Curated by eLife

  Evaluation Summary:

  By revealing different conformational landscapes of EGFR when responding to different types of ligands, this study significantly advances our understanding the structural basis for how EGFR generates distinct downstream signaling in response to different types of ligands. This study represents an important advance in the field and paves the way for the comprehensive understanding of structural mechanisms underlying biased agonism in EGFR and other RTKs.

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

Reviewed by eLife

NUDT18 catalyzes the hydrolysis of active metabolites of the antivirals Remdesivir, Ribavirin and Molnupiravir

1. Ann-Sofie Jemth
2. Emma Rose Scaletti
3. Evert Homan
4. Pål Stenmark
5. Thomas Helleday
6. Maurice Michel

Reviewed by ScreenIT

A Potential Novel COVID-19 Vaccine With RBD-HR1/HR2 Hexamer Structure

1. Hongbo Liu
2. Xiang Gao
3. Guoyong Wang
4. Jianjun Zhang
5. Jiajie Zhou
6. Tingting Wei
7. Yu Zhang
8. Yujiao Liu
9. Jinhua Piao
10. Qiulei Zhang
11. Yayuan Wang
12. Xin Ma
13. Xiaoting Zhu
14. Yikun Rao
15. Wenjuan Xia
16. Heng Xie
17. Wei Zhang

Reviewed by ScreenIT

Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological, and pathological disease in a Syrian hamster model of COVID-19

1. Thomas J. Esparza
2. Yaozong Chen
3. Negin P. Martin
4. Helle Bielefeldt-Ohmann
5. Richard A. Bowen
6. William D. Tolbert
7. Marzena Pazgier
8. David L. Brody

Reviewed by ScreenIT

Design of D-Amino Acids SARS-CoV-2 Main Protease Inhibitors Using the Cationic Peptide from Rattlesnake Venom as a Scaffold

1. Raphael J. Eberle
2. Ian Gering
3. Markus Tusche
4. Philipp N. Ostermann
5. Lisa Müller
6. Ortwin Adams
7. Heiner Schaal
8. Danilo S. Olivier
9. Marcos S. Amaral
10. Raghuvir K. Arni
11. Dieter Willbold
12. Mônika A. Coronado

Reviewed by ScreenIT

Allosteric mechanism of signal transduction in the two-component system histidine kinase PhoQ

1. Bruk Mensa
2. Nicholas F Polizzi
3. Kathleen S Molnar
4. Andrew M Natale
5. Thomas Lemmin
6. William F DeGrado

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to scientists who think about mechanisms of conformational signaling within transmembrane receptor proteins. It describes a model of signaling by allosteric coupling between individual domains rather than by a concerted conformational change and provides substantial experimental evidence for the model from characterization of over 30 mutational substitutions in the bacterial two-component sensor protein PhoQ. The allosteric coupling model provides a way to understand many diverse observations about signaling by two-component receptors and has the potential to be relevant to conformational signaling by many other transmembrane 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

Heavy isotope labeling and mass spectrometry reveal unexpected remodeling of bacterial cell wall expansion in response to drugs

1. Heiner Atze
2. Yucheng Liang
3. Jean-Emmanuel Hugonnet
4. Arnaud Gutierrez
5. Filippo Rusconi
6. Michel Arthur

• Curated by eLife

  Evaluation Summary:

  The authors describe the innovative use of a heavy-isotope labeling strategy combined with mass spectrometry analysis to investigate the role of peptidoglycan biosynthesis by an L,D-transpeptidase and penicillin binding proteins in Escherichia coli. They use isotopic labeling of the peptidoglycan following by a chase experiment with label to study how new peptidoglycan is assembled into pre-existing peptidoglycan. The data suggests that new material is inserted one strand at the time on the lateral wall while it appears to be inserted as multiple strands at the division septum. The data are novel and provide important insights, together with notable methodological advances. The study will be of interest to microbiologists studying bacterial cell wall turnover and for drug discovery efforts.

  (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

Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

1. Dylan Gerard Ryan
2. Ming Yang
3. Hiran A Prag
4. Giovanny Rodriguez Blanco
5. Efterpi Nikitopoulou
6. Marc Segarra-Mondejar
7. Christopher A Powell
8. Tim Young
9. Nils Burger
10. Jan Lj Miljkovic
11. Michal Minczuk
12. Michael P Murphy
13. Alex von Kriegsheim
14. Christian Frezza

• Curated by eLife

  Evaluation Summary:

  The authors of this study investigate the consequences of acute or chronic disruption of parts of the TCA cycle, and how different interventions can drive different transcriptional responses. Specifically, the authors use both pharmacological and genetic methods to disrupt succinate dehydrogenase or fumarate hydratase, and characterize the effect of each on metabolism. They also find that disruption of these enzymes elicits a transcriptional response through ATF4. This work provides insight into how metabolism is affected by TCA cycle loss, and how how this affects metabolic stress 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 #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Disintegration promotes protospacer integration by the Cas1-Cas2 complex

1. Chien-Hui Ma
2. Kamyab Javanmardi
3. Ilya J Finkelstein
4. Makkuni Jayaram

• Curated by eLife

  Evaluation Summary:

  In this manuscript, an in vitro Cas1-Cas2 model system is used to study the reaction used to insert foreign DNA elements into a CRISPR array during the adaptive phase of immunity. The authors propose that hydrolysis of one end of the transposon DNA may be the primary mechanism for the insertion of very small DNA elements (which are difficult to bend tightly) that are found for the proto spacer sequences, and that cellular repair pathways are responsible for ligating the CRISPR array back together in vivo. The findings additionally suggest that water-mediated disintegration has an unappreciated role in the generation of CRISPR arrays as part of the bacterial immune response. These hypotheses are intriguing and of potential interest to those in the CRISPR field. However, it is unclear how this in vitro study, which does not monitor the full the reaction (directionality is lost due to the lack of a PAM sequence in the substrate and several required cellular factors are missing), relates to transposition as it occurs in vivo. Overall, this is an interesting study that challenges the current thinking in the field, but it does not present sufficient evidence to establish the physiological significance of the observed effects, thereby limiting its potential broader impact.

  (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