eLife

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1. Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery

   This article has 13 authors:

   1. Dmitry Shvarev
   2. Jannis Schoppe
   3. Caroline König
   4. Angela Perz
   5. Nadia Füllbrunn
   6. Stephan Kiontke
   7. Lars Langemeyer
   8. Dovile Januliene
   9. Kilian Schnelle
   10. Daniel Kümmel
   11. Florian Fröhlich
   12. Arne Moeller
   13. Christian Ungermann

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript reports the cryo-EM structure of HOPS, a heterohexameric tether that participates in the fusion of late endosomes, autophagosomes, and AP-3 vesicles with lysosomes. The structure will be of interest to a wide range of cell biologists and structural biologists who study membrane traffic. However, while the structural data are elegant, the functional interpretations need further support.

     (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

2. Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

   This article has 10 authors:

   1. Yitong Li
   2. Vijaya Kumar Balakrishnan
   3. Michael Rowse
   4. Cheng-Guo Wu
   5. Anastasia Phoebe Bravos
   6. Vikash K Yadav
   7. Ylva Ivarsson
   8. Stefan Strack
   9. Irina V Novikova
   10. Yongna Xing

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Xing and colleagues present a cryoEM structure of the protein phosphatase 2A (PP2A)-B56 holoenzyme in complex with protein phosphatase methyltransferase-1 (PME-1). The structure reveals that PME-1 blocks the substrate binding site of PP2A by inserting an unstructured loop. This unexpected inhibitory mechanism is also coupled to a large conformation change in the PP2A-B56 holoenzyme and PME-1. Combined with biochemical and cellular assays, the authors suggest how PME-1 can regulate p53-mediated DNA damage responses via inhibiting PP2A. This manuscript will be of importance for structural biologists as well as colleagues in the p53 field.

     (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

3. The evolution of a counter-defense mechanism in a virus constrains its host range

   This article has 3 authors:

   1. Sriram Srikant
   2. Chantal K Guegler
   3. Michael T Laub

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript will be of interest to researchers in the phage-microbial host interaction field. Notably, the interplay between bacteria and their viral predators has regained broad interest in recent years given the discovery of numerous innate immunity-like phage defense systems. The identification of phage-mediated counter-defense strategies is therefore not only of prime importance for our basic understanding of predator-prey arms races but also for medical applications such as phage therapy.

     (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

4. Membrane-mediated dimerization potentiates PIP5K lipid kinase activity

   This article has 4 authors:

   1. Scott D Hansen
   2. Albert A Lee
   3. Benjamin R Duewell
   4. Jay T Groves

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper is of interest for a wide range of readers who study the biology of lipid modifying enzymes, especially as it relates to interfacial reaction kinetics in biological membranes. This study aimed to obtain detailed biochemical insights into the mutual relationship between PI(4,5)P2 lipids and their kinase PIP5K, which engage in an exciting pattern-forming reaction on membranes. The authors find cooperative recruitment of PIP5K to the membrane, oligomerization-enhanced catalytic efficiency and indications of allosteric regulation. Although of very high interest and featuring mostly convincing data, there are concerns about the interpretation of whether the observed phenomenon is dimer specific or related to higher-order oligomerization. In addition, there are inconsistencies in the data presentation.

     (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

5. An auto-inhibited state of protein kinase G and implications for selective activation

   This article has 13 authors:

   1. Rajesh Sharma
   2. Jeong Joo Kim
   3. Liying Qin
   4. Philipp Henning
   5. Madoka Akimoto
   6. Bryan VanSchouwen
   7. Gundeep Kaur
   8. Banumathi Sankaran
   9. Kevin R MacKenzie
   10. Giuseppe Melacini
   11. Darren E Casteel
   12. Friedrich W Herberg
   13. Choel Kim

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This reported crystal structure of nearly-full-length cGMP-dependent protein kinase β (PGK1β) provides new insights into how the activity of the PKG catalytic domain is held in check by intramolecular interactions between both the upstream regulatory cGMP-binding domains and the autoinhibitory segment and the catalytic domain, and how cGMP binding to the cGMP-binding domains can relieve these inhibitory constraints leading to an increase in catalytic activity. The structure of the activating PKGIα R177Q CNB-A domain mutant, which resembles a cGMP-bound wild type CNB-A domain, provides a nice explanation for how this point mutation activates PKG Iα and leads to the development of the TAAD (Thoracic Aortic Aneurysms and Dissections) syndrome. The work will be of specific interest to the cyclic nucleotide community, and to the broader signaling community in general.

     (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

6. Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state

   This article has 16 authors:

   1. Caterina Carraro
   2. Lorenzo Bonaguro
   3. Jonas Schulte-Schrepping
   4. Arik Horne
   5. Marie Oestreich
   6. Stefanie Warnat-Herresthal
   7. Tim Helbing
   8. Michele De Franco
   9. Kristian Haendler
   10. Sach Mukherjee
   11. Thomas Ulas
   12. Valentina Gandin
   13. Richard Goettlich
   14. Anna C Aschenbrenner
   15. Joachim L Schultze
   16. Barbara Gatto

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This article applies a systems biology approach to understand the mechanism of action of 3-chloropiperidines (a class of anticancer drugs) in cancer cells and evaluate their sensitivity to drugs. It integrates transcriptomic and open-chromatin data and utilizes sound statistical frameworks for building a sensitivity model. The author's methodology can be applied to early-stage drug discovery. This paper will be of interest to the large class of people who tried to understand how omics data will help drug discovery. It sets a new framework to integrate transcriptome and chromatin accessibility data to identify the key mechanisms of action and provide potential disease targets, which will help speed up the early phases of drug discovery.

     (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. All three reviewers agreed to share their names with the authors.)

   Reviewed by eLife

7. A single-cell atlas of the cycling murine ovary

   This article has 13 authors:

   1. Mary E Morris
   2. Marie-Charlotte Meinsohn
   3. Maeva Chauvin
   4. Hatice D Saatcioglu
   5. Aki Kashiwagi
   6. Natalie A Sicher
   7. Ngoc Nguyen
   8. Selena Yuan
   9. Rhian Stavely
   10. Minsuk Hyun
   11. Patricia K Donahoe
   12. Bernardo L Sabatini
   13. David Pépin

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study is of interest to the readership interested in the different cell types present in the mouse adult ovary and shows how cellular states change during the four phases of the estrous cycle. This is a valuable resource for the community.

     (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

8. A method for low-coverage single-gamete sequence analysis demonstrates adherence to Mendel’s first law across a large sample of human sperm

   This article has 7 authors:

   1. Sara A Carioscia
   2. Kathryn J Weaver
   3. Andrew N Bortvin
   4. Hao Pan
   5. Daniel Ariad
   6. Avery Davis Bell
   7. Rajiv C McCoy

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The authors first develop a new flexible and robust method to detect deviations from Mendelian inheritance in genomic data from gametes. The authors then apply this method to study deviations from Mendelian inheritance in human sperm data, but find no evidence for it. Even though this is a negative result, and overall the results are expected based on previous studies. the reviewers agreed that the research is rigorous and valuable.

     (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

9. PH domain-mediated autoinhibition and oncogenic activation of Akt

   This article has 8 authors:

   1. Hwan Bae
   2. Thibault Viennet
   3. Eunyoung Park
   4. Nam Chu
   5. Antonieta Salguero
   6. Michael J Eck
   7. Haribabu Arthanari
   8. Philip A Cole

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Bae et al. examine the regulatory role of the PH domain of the AKT Ser/ Thr kinase, finding a key set of interactions that mediate autoinhibitory interactions between PH and kinase domains. The work provides additional mechanistic understanding of the E17K mutation, a common variant in human cancers. This manuscript will be of great interest to scientists focused on protein kinase regulation and molecular mechanisms that control signal transduction.

     (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

10. Decoding mitochondrial genes in pediatric AML and development of a novel prognostic mitochondrial gene signature

    This article has 8 authors:

    1. Shilpi Chaudhary
    2. Shuvadeep Ganguly
    3. Jayanth Kumar Palanichamy
    4. Archna Singh
    5. Dibyabhaba Pradhan
    6. Radhika Bakhshi
    7. Anita Chopra
    8. Sameer Bakhshi

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      Chaudhary and colleagues follow up their preliminary study on mitochondrial genome copy number in AML with this current study by looking if the expression of specific genes encoding mitochondrial components could provide further insight into AML prognosis. Multivariate analysis was used to identify those genes whose expression was prognostic of patient outcome, which led to the identification of three mitochondrial genes whose expression was used to build a multivariate risk model for childhood AML patients. Altogether, the work by Chaudhary and colleagues interestingly builds on their previous work and suggests that mitochondria may influence AML outcomes, and measuring mitochondrial parameters may help assess patient risk. However, the authors will need to identify the novelty of their findings over the previous reports from their own group.

      (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