Biochemistry

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

Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission

1. Dawn M Wenzel
2. Douglas R Mackay
3. Jack J Skalicky
4. Elliott L Paine
5. Matthew S Miller
6. Katharine S Ullman
7. Wesley I Sundquist

• Curated by eLife

  Evaluation Summary:

  The authors quantitatively characterize binding interactions between all known MIM motifs of ESCRT-III proteins with the MIT motifs of several AAA+ ATPases. In addition to the analysis of these interactions, which will be an important resource to the ESCRT community, the authors also identify new roles of the ATPases SPASTIN, KATNA1 and CAPN7 in cytokinesis. Therefore, the work will be of broad interest to biologists interested in membrane-associated complexes and in cell cycle and cytokinesis.

  (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 names with the authors.)

Reviewed by eLife

Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes

1. Edhriz Siraliev-Perez
2. Jordan TB Stariha
3. Reece M Hoffmann
4. Brenda RS Temple
5. Qisheng Zhang
6. Nicole Hajicek
7. Meredith L Jenkins
8. John E Burke
9. John Sondek

• Curated by eLife

  Evaluation Summary:

  This work provides insight into how phospholipase C gamma (PLCγ1) becomes activated upon binding to phosphorylated receptor tyrosine kinase, with an analysis of PLC γ1 bound to the soluble kinase domain of FGFR1 (FGFR1K) and/or liposomes containing PIP2. The most interesting finding is that regions of the protein far from the FGFR1K binding site increase in exchange upon binding. This is new information for a large protein that is arguably difficult to study, but it conforms to what has been observed in many other autoinhibited systems with similar SH2 and SH3 domains such as kinases. The results will be of interest to structural biologists and cell biologists with interest in the mechanisms leading to the regulation of phospholipase C activity on membranes.

  (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

Hypertrophic cardiomyopathy mutations in the pliant and light chain-binding regions of the lever arm of human β-cardiac myosin have divergent effects on myosin function

1. Makenna M Morck
2. Debanjan Bhowmik
3. Divya Pathak
4. Aminah Dawood
5. James Spudich
6. Kathleen M Ruppel

• Curated by eLife

  Evaluation Summary:

  This work is of broad interest to readers in the fields of cytoskeletal research, muscle biology and heart disease. By utilizing a combination of quantitative biochemical and biophysical experimental approaches, this work provides critical new insights into the molecular mechanisms of understudied mutations in myosin that cause heart disease. The data are rigorously controlled and analyzed and support the claims of the work.

  (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

Structural basis for RNA-duplex unwinding by the DEAD-box helicase DbpA

1. Jan Philip Wurm

• Curated by eLife

  Evaluation Summary:

  This manuscript is interesting to a broad audience in the general fields of RNA and structural biology. It provides detailed and important molecular insight into one of the mechanisms by which ATP-fueled RNA helicases can cause the local destabilisation of terminal base-pairs and eventually contribute to RNA structure remodelling and it is a prime example of how crystallographic high-resolution snapshots of conformational intermediates can be combined with sophisticated NMR techniques and assays into a comprehensive model. The manuscript would benefit from a broader and more explicit comparative discussion including the limitations of the proposed model, because DbpA is a rather specialised RNA helicase and because the double-stranded RNA substrates were specifically designed to exclusively investigate unwinding from the side of a short 5'-overhang.

  (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

Antibacterial potency of type VI amidase effector toxins is dependent on substrate topology and cellular context

1. Atanas Radkov
2. Anne L Sapiro
3. Sebastian Flores
4. Corey Henderson
5. Hayden Saunders
6. Rachel Kim
7. Steven Massa
8. Samuel Thompson
9. Chase Mateusiak
10. Jacob Biboy
11. Ziyi Zhao
12. Lea M Starita
13. William L Hatleberg
14. Waldemar Vollmer
15. Alistair B Russell
16. Jean-Pierre Simorre
17. Spencer Anthony-Cahill
18. Peter Brzovic
19. Beth Hayes
20. Seemay Chou

Reviewed by Review Commons