Biochemistry

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

1. Palur V Raghuvamsi
2. Nikhil K Tulsian
3. Firdaus Samsudin
4. Xinlei Qian
5. Kiren Purushotorman
6. Gu Yue
7. Mary M Kozma
8. Wong Y Hwa
9. Julien Lescar
10. Peter J Bond
11. Paul A MacAry
12. Ganesh S Anand

• Curated by eLife

  Summary: This is a timely and interesting exploration of the interaction between the Spike protein of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, and the ACE2 receptor using hydrogen deuterium exchange mass spectrometry and molecular dynamics simulations. The Spike protein consists of two sub-domains S1 and S2 with the S1 needing to be cleaved-off so the S2 can become the fusion protein responsible for getting the SARS-CoV-2 into the cell. Structures are available but they do not shed light on how the protease furin can access the cleavage site between S1 and S2 in order to begin the process of fusion. The results suggest that the Spike-ACE2 interaction induces extremely long-range allosteric effects on the Spike protein that could trigger proteolysis of the Spike protein. Specifically, when ACE2 binds to the Spike protein, a conformational change occurs near the S1/S2 cleavage site, exposing it and likely making it more susceptible to furin cleavage. The binding also dampens exchange in the stalk region of the Spike protein. The authors refer to these regions as "dynamic hotspots in the pre-fusion state". The results of this work have implications for the development of small molecule inhibitors.

  In general, the work is timely, and the results will be of interest to many in the field. The major conclusions of the work are generally supported by the results.

Reviewed by eLife, ScreenIT

A computationally designed fluorescent biosensor for D-serine

1. Vanessa Vongsouthi
2. Jason H. Whitfield
3. Petr Unichenko
4. Joshua A. Mitchell
5. Björn Breithausen
6. Olga Khersonsky
7. Leon Kremers
8. Harald Janovjak
9. Hiromu Monai
10. Hajime Hirase
11. Sarel J. Fleishman
12. Christian Henneberger
13. Colin J. Jackson

• Curated by eLife

  Summary: The reviewers recognize the merits of your work and your efforts to engineer a D-serine selective biosensor. However, they also raise major concerns regarding the experimental design (selection of mutations), methodology and achieved applicability. The reviewers find that the improvement in the selectivity of the engineered construct for the targeted ligand over alternative ligands is modest. They further indicate ambiguities regarding the origin of the ligand-induced fluorescence signal changes of the sensor. Other problematic aspects are the estimation of thermal stabilities and the lack of physiological signals in fluorescence imaging results that could demonstrate applicability to a biological problem.

Reviewed by eLife

Hypoxia-inducible lipid droplet-associated interacts with DGAT1 and promotes lipid storage in hepatocytes

1. Montserrat A. de la Rosa Rodriguez
2. Anne Gemmink
3. Michel van Weeghel
4. Marie Louise Aoun
5. Christina Warnecke
6. Rajat Singh
7. Jan Willem Borst
8. Sander Kersten

Reviewed by eLife

Rqc1 and other yeast proteins containing highly positively charged sequences are not targets of the RQC complex

1. Géssica C. Barros
2. Rodrigo D. Requião
3. Rodolfo L. Carneiro
4. Claudio A. Masuda
5. Mariana H. Moreira
6. Silvana Rossetto
7. Tatiana Domitrovic
8. Fernando L. Palhano

Reviewed by eLife

The linear ubiquitin chain assembly complex LUBAC generates heterotypic ubiquitin chains

1. Alan Rodriguez Carvajal
2. Carlos Gomez Diaz
3. Antonia Vogel
4. Adar Sonn-Segev
5. Katrin Schodl
6. Luiza Deszcz
7. Zsuzsanna Orban-Nemeth
8. Shinji Sakamoto
9. Karl Mechtler
10. Philipp Kukura
11. Tim Clausen
12. David Haselbach
13. Fumiyo Ikeda

Reviewed by eLife

Metabolomics and lipidomics in C. elegans using a single sample preparation

1. Marte Molenaars
2. Bauke V. Schomakers
3. Hyung L. Elfrink
4. Arwen W. Gao
5. Martin A.T. Vervaart
6. Mia L. Pras-Raves
7. Angela C. Luyf
8. Reuben L. Smith
9. Mark G. Sterken
10. Jan E. Kammenga
11. Antoine H. C. van Kampen
12. Georges E. Janssens
13. Frédéric M. Vaz
14. Michel van Weeghel
15. Riekelt H. Houtkooper

Reviewed by Review Commons

An SNP variant MT1-MMP with a defect in its collagenolytic activity confers the fibrotic phenotype of Dupuytren’s Disease

1. Yoshifumi Itoh
2. Michael Ng
3. Akira Wiberg
4. Katsuaki Inoue
5. Narumi Hirata
6. Katiucia Batista Silva Paiva
7. Noriko Ito
8. Kim Dzobo
9. Nanami Sato
10. Valentina Gifford
11. Yasuyuki Fujita
12. Masaki Inada
13. Dominic Furniss

Reviewed by eLife

Diversity of function and higher-order structure within HWE sensor histidine kinases

1. Igor Dikiy
2. Danielle Swingle
3. Kaitlyn Toy
4. Uthama R. Edupuganti
5. Giomar Rivera-Cancel
6. Kevin H. Gardner

Reviewed by eLife

An Atlas of Phosphorylation and Proteolytic Processing Events During Excitotoxic Neuronal Death Reveals New Therapeutic Opportunities

1. S. Sadia Ameen
2. Antoine Dufour
3. M. Iqbal Hossain
4. Ashfaqul Hoque
5. Sharelle Sturgeon
6. Harshal Nandurkar
7. Dominik Draxler
8. Robert Medcalf
9. Mohd Aizuddin Kamaruddin
10. Isabelle S. Lucet
11. Michael G. Leeming
12. Dazhi Liu
13. Amardeep Dhillon
14. Jet Phey Lim
15. Hong-Jian Zhu
16. Laita Bokhari
17. Carli Roulston
18. Oded Kleifeld
19. D. Ciccotosto Giuseppe
20. Nicholas A. Williamson
21. Ching-Seng Ang
22. Heung-Chin Cheng

Reviewed by Review Commons

Peroxisomes contribute to intracellular calcium dynamics

1. Yelena Sargsyan
2. Uta Bickmeyer
3. Katrin Streckfuss-Bömeke
4. Ivan Bogeski
5. Sven Thoms

Reviewed by Review Commons