Biochemistry

The orphan ligand, activin C, signals through activin receptor-like kinase 7

1. Erich J Goebel
2. Luisina Ongaro
3. Emily C Kappes
4. Kylie Vestal
5. Elitza Belcheva
6. Roselyne Castonguay
7. Ravindra Kumar
8. Daniel J Bernard
9. Thomas B Thompson

• Curated by eLife

  Evaluation Summary:

  This study was designed to examine the orphan ligand ActivinC. The authors show that ActivinC signals through ALK7. The data presented are strong and convincing. Indeed, the use of purified proteins for the interaction assays and in vivo analysis of adipocytes provide considerable rigor to the analysis. The work will be of interest to the areas of signal transduction and drug design.

  (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 agreed to share their name with the authors.)

Reviewed by eLife

Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

1. Wayne Mitchell
2. Jeffrey D Tamucci
3. Emery L Ng
4. Shaoyi Liu
5. Alexander V Birk
6. Hazel H Szeto
7. Eric R May
8. Andrei T Alexandrescu
9. Nathan N Alder

• Curated by eLife

  Evaluation Summary:

  Wayne Mitchell et al. report the study aimed to determine the structural features of cationic hydrophobic tetrapeptides in their cytoprotective efficacy. Detailed structural characterization of the peptides "free" in solution and bound to membranes is followed by their comparison in protecting cells from starvation-induced stress and the loss of viability. Overall, there are important and detailed observations regarding the peptide-membrane interactions, while their relevance to cytoprotection mechanisms in not demonstrated.

  (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 agreed to share their name with the authors.)

Reviewed by eLife

Reconstitution of the SARS-CoV-2 ribonucleosome provides insights into genomic RNA packaging and regulation by phosphorylation

1. Christopher R. Carlson
2. Armin N. Adly
3. Maxine Bi
4. Conor J. Howard
5. Adam Frost
6. Yifan Cheng
7. David O. Morgan

Reviewed by ScreenIT

Structure of Mycobacterium tuberculosis Cya, an evolutionary ancestor of the mammalian membrane adenylyl cyclases

1. Ved Mehta
2. Basavraj Khanppnavar
3. Dina Schuster
4. Ilayda Kantarci
5. Irene Vercellino
6. Angela Kosturanova
7. Tarun Iype
8. Sasa Stefanic
9. Paola Picotti
10. Volodymyr M Korkhov

• Curated by eLife

  Evaluation Summary:

  This manuscript reports the first full-length structure of membrane-bound adenylyl cyclase from the pathogen Mycobacterium tuberculosis. The structure provides insights into its potential mechanism of action and reveals similarities to its mammalian counterpart. Thus, this paper is of potential interest to a broad audience including the fields of infectious diseases, signaling, and evolutionary biologists.

  (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

A dual-target herbicidal inhibitor of lysine biosynthesis

1. Emily RR Mackie
2. Andrew S Barrow
3. Rebecca M Christoff
4. Belinda M Abbott
5. Anthony R Gendall
6. Tatiana P Soares da Costa

• Curated by eLife

  Evaluation Summary:

  This excellent paper presents the highly interesting finding of a compound that inhibits two targets in lysine synthesis. Further, the mechanisms for the first enzyme is allosteric inhibition, while for the second enzyme the compound is a competitive inhibitor. The authors nicely explain why this is of significant interest for herbicide resistance management with a new compound. The authors convincingly demonstrate that the compound is not a pro-herbicide, and instead that the higher in vivo relative to in vitro activity is due to the additional inhibition of the second step in lysine synthesis. The work is of interest to those studying enzymology, herbicide action and evolution of herbicide resistance.

  (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 #2 agreed to share their names with the authors.)

Reviewed by eLife

Conserved structural elements specialize ATAD1 as a membrane protein extraction machine

1. Lan Wang
2. Hannah Toutkoushian
3. Vladislav Belyy
4. Claire Y Kokontis
5. Peter Walter

• Curated by eLife

  Evaluation Summary:

  This work extends our understanding of the ATAD1 family of AAA proteins responsible for extracting tail-anchored (TA) proteins mistargeted to the mitochondria. The conclusions of this work are largely consistent to prior structural studies from the same group, but provide clarifications of specific details that will be of interest to those working on these important proteins.

  (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

DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes

1. Sudipta Mondal
2. Priyadarshan Kinatukara
3. Shubham Singh
4. Sakshi Shambhavi
5. Gajanan S Patil
6. Noopur Dubey
7. Salam Herojeet Singh
8. Biswajit Pal
9. P Chandra Shekar
10. Siddhesh S Kamat
11. Rajan Sankaranarayanan

• Curated by eLife

  Evaluation Summary:

  The DISCO-interacting protein 2 (DIP2) family consists of poorly characterized proteins linked to lipid metabolism, with a previously unclear role in cell physiology. DIP2 proteins contain putative fatty acyl-AMP ligase domains (FAALs), which are thought to influence fatty acid activation and attachment to various metabolites. Here, the authors analyze the role of budding yeast ScDIP2, and propose that it regulates a specific sub-pool of diacylglycerol (DAG) lipids and their conversion into storage triglycerides. While the exact molecular mechanism is not clear yet, this study will be of interest to cell biologists interested in lipids, metabolism, and ER stress.

  (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

Molecular dynamics of spike variants in the locked conformation: RBD interfaces, fatty acid binding and furin cleavage sites

1. Deborah K. Shoemark
2. A. Sofia F. Oliveira
3. Andrew D. Davidson
4. Imre Berger
5. Christiane Schaffitzel
6. Adrian J. Mulholland

Reviewed by ScreenIT

Cryo-EM structures reveal that RFC recognizes both the 3′- and 5′-DNA ends to load PCNA onto gaps for DNA repair

1. Fengwei Zheng
2. Roxana Georgescu
3. Nina Y Yao
4. Huilin Li
5. Michael E O'Donnell

• Curated by eLife

  Evaluation Summary:

  The role of Replication Factor C (RFC) in DNA replication and repair has been known for many years. RFC/PCNA binds to a double strand-single strand DNA junction with a 3'-recessed end, with the DNA passing through a central chamber in the five-subunit protein. The current paper reports structures of RFC/PCNA with two separate DNA molecules, one containing the well characterized 3'-recessed DNA and surprisingly, a second 5'-recessed DNA outside the central chamber.The paper is an important addition to understanding RFC function, particularly in DNA repair, but it could be improved with some clarifications. The work is of interest to all studying DNA replication.

  (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, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

A Novel Y-Shaped, S-O-N-O-S-Bridged Crosslink between Three Residues C22, C44, and K61 Is a Redox Switch of the SARS-CoV-2 Main Protease

1. Kai S. Yang
2. Syuan-Ting Alex Kuo
3. Lauren R. Blankenship
4. Yan J. Sheng
5. Banumathi Sankaran
6. Pingwei Li
7. Carol A. Fierke
8. David H. Russell
9. Xin Yan
10. Shiqing Xu
11. Wenshe Ray Liu

Reviewed by ScreenIT