Biochemistry

Towards a molecular mechanism underlying mitochondrial protein import through the TOM and TIM23 complexes

1. Holly C Ford
2. William J Allen
3. Gonçalo C Pereira
4. Xia Liu
5. Mark Simon Dillingham
6. Ian Collinson

• Curated by eLife

  Evaluation Summary:

  This study employs a novel bioluminescence-based technique to analyze the import of precursor proteins into the mitochondrial matrix in real time. This is an innovative technical advance that can provide mechanistic detail on the kinetic steps of mitochondrial protein import. It has potential applications in other membrane protein transport systems and it could be applicable to studies in applied science such as screening for drugs targeting the mitochondrial import apparatus.

  (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 name with the authors.)

Reviewed by eLife

Autoinhibition and regulation by phosphoinositides of ATP8B1, a human lipid flippase associated with intrahepatic cholestatic disorders

1. Thibaud Dieudonné
2. Sara Abad Herrera
3. Michelle Juknaviciute Laursen
4. Maylis Lejeune
5. Charlott Stock
6. Kahina Slimani
7. Christine Jaxel
8. Joseph A Lyons
9. Cédric Montigny
10. Thomas Günther Pomorski
11. Poul Nissen
12. Guillaume Lenoir

• Curated by eLife

  Evaluation Summary:

  This manuscript reports the first high-resolution structure of the P4 flippase ATP8B1, which is associated with intrahepatic cholestatic disorder in humans. Using biochemical studies guided by the structure, the authors demonstrate ATP8B1's autoinhibition mechanism, its regulation by lipids and phosphorylation, and a plausible mechanism of disease-associated mutation. These results are an important contribution to the expanding literature in membrane protein dynamics and 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

Structure-Based Identification of Naphthoquinones and Derivatives as Novel Inhibitors of Main Protease M ^pro and Papain-like Protease PL ^pro of SARS-CoV-2

1. Lucianna H. Santos
2. Thales Kronenberger
3. Renata G. Almeida
4. Elany B. Silva
5. Rafael E. O. Rocha
6. Joyce C. Oliveira
7. Luiza V. Barreto
8. Danielle Skinner
9. Pavla Fajtová
10. Miriam A. Giardini
11. Brendon Woodworth
12. Conner Bardine
13. André L. Lourenço
14. Charles S. Craik
15. Antti Poso
16. Larissa M. Podust
17. James H. McKerrow
18. Jair L. Siqueira-Neto
19. Anthony J. O’Donoghue
20. Eufrânio N. da Silva Júnior
21. Rafaela S. Ferreira

Reviewed by ScreenIT

Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement

1. Matthew McCallum
2. Nadine Czudnochowski
3. Laura E. Rosen
4. Samantha K. Zepeda
5. John E. Bowen
6. Alexandra C. Walls
7. Kevin Hauser
8. Anshu Joshi
9. Cameron Stewart
10. Josh R. Dillen
11. Abigail E. Powell
12. Tristan I. Croll
13. Jay Nix
14. Herbert W. Virgin
15. Davide Corti
16. Gyorgy Snell
17. David Veesler

Reviewed by ScreenIT

Mapping the allosteric effects that define functional activity of SARS-CoV-2 specific antibodies

1. Nikhil K. Tulsian
2. Palur V. Raghuvamsi
3. Xinlei Qian
4. Gu Yue
5. Bhuvaneshwari D/O Shunmuganathan
6. Firdaus Samsudin
7. Wong Yee Hwa
8. Lin Jianqing
9. Kiren Purushotorman
10. Mary M. Kozma
11. Bei Wang
12. Julien Lescar
13. Cheng-I Wang
14. Ganesh S. Anand
15. Peter J. Bond
16. Paul A. MacAry

Reviewed by ScreenIT

The SARS-CoV-2 nucleocapsid protein preferentially binds long and structured RNAs

1. Christen E. Tai
2. Einav Tayeb-Fligelman
3. Sarah Griner
4. Lukasz Salwinski
5. Jeannette T. Bowler
6. Romany Abskharon
7. Xinyi Cheng
8. Paul M. Seidler
9. Yi Xiao Jiang
10. David S. Eisenberg
11. Feng Guo

Reviewed by ScreenIT

In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding

1. Neil Bate
2. Christos G. Savva
3. Peter C. E. Moody
4. Edward A. Brown
5. Sian E. Evans
6. Jonathan K. Ball
7. John W. R. Schwabe
8. Julian E. Sale
9. Nicholas P. J. Brindle

Reviewed by ScreenIT

Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation

1. Kristina V. Tugaeva
2. Andrey A. Sysoev
3. Anna A. Kapitonova
4. Jake L.R. Smith
5. Phillip Zhu
6. Richard B. Cooley
7. Alfred A. Antson
8. Nikolai N. Sluchanko

Reviewed by ScreenIT

METTL3 promotes homologous recombination repair and modulates chemotherapeutic response in breast cancer by regulating the EGF/RAD51 axis

1. Enjie Li
2. Mingyue Xia
3. Yu Du
4. Kaili Long
5. Feng Ji
6. Feiyan Pan
7. Lingfeng He
8. Zhigang Hu
9. Zhigang Guo

• Curated by eLife

  Evaluation Summary:

  The potential mechanism of METTL3 N6-methyltransferase in the chemotherapeutic response is poorly defined. Herein, Li and colleagues describe a pathway where METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity. METTL3 knockdown results in DNA damage accumulation, which renders breast cancer cells sensitive to adriamycin treatment.

  (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

The N -Terminal Carbamate is Key to High Cellular and Antiviral Potency for Boceprevir-Based SARS-CoV-2 Main Protease Inhibitors

1. Yugendar R. Alugubelli
2. Zhi Zachary Geng
3. Kai S. Yang
4. Namir Shaabani
5. Kaustav Khatua
6. Xinyu R. Ma
7. Erol C. Vatansever
8. Chia-Chuan Cho
9. Yuying Ma
10. Lauren Blankenship
11. Ge Yu
12. Banumathi Sankaran
13. Pingwei Li
14. Robert Allen
15. Henry Ji
16. Shiqing Xu
17. Wenshe Ray Liu

Reviewed by ScreenIT