Biochemistry

Recapitulating the frataxin activation mechanism in an engineered bacterial cysteine desulfurase supports the architectural switch model

1. Shachin Patra
2. Cheng-Wei Lin
3. Manas K. Ghosh
4. Steven M. Havens
5. Seth A. Cory
6. David H. Russell
7. David P. Barondeau

• Curated by eLife

  Summary: This study provides support for a proposed allosteric regulatory mechanism in a human iron-sulfur cluster biosynthesis protein that is linked to the human genetic disorder, Friedrich's Ataxia. In an approach guided by inspection of a structure of the human enzyme, the authors successfully converted a bacterial homolog lacking allosteric regulation into a system that behaves similarly to the human one. The work provides validation of the roles of accessory proteins in activating iron-sulfur cluster biosynthesis machinery. It also could open novel routes for therapeutic intervention in genetic disorders of this process in humans.

  The major concerns about the study center on the significance of the form of the human enzyme structure used as the basis for designing the mutagenesis/activity experiments in the bacterial enzyme. To bolster the underlying framework for the experiment design, the description of the existing human enzyme structures and how exactly they were used to select sites for mutagenesis in the bacterial counterparts should be improved to include more detail and balanced perspective. Experiments are suggested to show that activity enhancement upon addition of accessory proteins is specific to those factors, along with a more comprehensive discussion of the errors and reproducibility in activity measurements. Finally, the significance of the work would be elevated if the authors could use a similar approach to install activating mutations in the human enzyme - particularly if these could overcome the requirement for frataxin.

Reviewed by eLife

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 induces DGAT1 and promotes lipid storage in hepatocytes

1. Montserrat A. de la Rosa Rodriguez
2. Lei Deng
3. Anne Gemmink
4. Michel van Weeghel
5. Marie Louise Aoun
6. Christina Warnecke
7. Rajat Singh
8. Jan Willem Borst
9. 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. Irina Grishkovskaya
3. Carlos Gomez Diaz
4. Antonia Vogel
5. Adar Sonn-Segev
6. Manish S Kushwah
7. Katrin Schodl
8. Luiza Deszcz
9. Zsuzsanna Orban-Nemeth
10. Shinji Sakamoto
11. Karl Mechtler
12. Philipp Kukura
13. Tim Clausen
14. David Haselbach
15. Fumiyo Ikeda

Reviewed by eLife

Metabolomics and lipidomics in Caenorhabditis 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

A common SNP risk variant MT1-MMP causative for Dupuytren's disease has a specific defect in collagenolytic activity

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