Biochemistry

Delta Variant with P681R Critical Mutation Revealed by Ultra-Large Atomic-Scale Ab Initio Simulation: Implications for the Fundamentals of Biomolecular Interactions

1. Puja Adhikari
2. Bahaa Jawad
3. Praveen Rao
4. Rudolf Podgornik
5. Wai-Yim Ching

Reviewed by ScreenIT

Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir

1. Sven Ullrich
2. Kasuni B. Ekanayake
3. Gottfried Otting
4. Christoph Nitsche

Reviewed by ScreenIT

Coiled coil control of growth factor and inhibitor-dependent EGFR trafficking and degradation

1. Deepto Mozumdar
2. Sol Hsun-Hui Chang
3. Kim Quach
4. Amy Doerner
5. Alanna Schepartz

• Curated by eLife

  Evaluation Summary:

  This manuscript investigates the cellular role of the juxtamembrane region in the EGF receptor, a poorly understood portion of the EGFR cytosolic domain that connects the transmembrane segment to the kinase domain. Through a series of well-designed experiments, the work shows that the endocytic trafficking route of EGFR following its activation is determined by the juxtamembrane coiled-coil conformation in a model cell line. This finding is important for three reasons. It identifies a critical role for the juxtamembrane region; it resolves the discrepancy that TGF-beta dissociation from EGFR is supposed to occur at higher pH, yet the EGFR-TGF-beta complex continues to signal from endosomes; and it pinpoints the mechanism of EGFR inhibition by a new class of tyrosine kinase inhibitors.

  (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. All reviewers agreed to share their names with the authors.)

Reviewed by eLife

Stabilization of the SARS-CoV-2 receptor binding domain by protein core redesign and deep mutational scanning

1. Alison C Leonard
2. Jonathan J Weinstein
3. Paul J Steiner
4. Annette H Erbse
5. Sarel J Fleishman
6. Timothy A Whitehead

Reviewed by ScreenIT

Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

1. Saba Islam
2. Mirren Charnley
3. Guneet Bindra
4. Julian Ratcliffe
5. Jiangtao Zhou
6. Raffaele Mezzenga
7. Mark Hulett
8. Kyunghoon Han
9. Joshua T. Berryman
10. Nicholas P. Reynolds

Reviewed by ScreenIT

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