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  1. Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C

    This article has 6 authors:
    1. Alexander S. Baier
    2. Nathan Gioacchini
    3. Priit Eek
    4. Erik M. Leith
    5. Song Tan
    6. Craig L. Peterson
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript presents an important analysis of the role that the nucleosome acidic patch plays in SWR1-catalyzed histone exchange. This manuscript contains convincing data which significantly expands our understanding of the complex process of H2A.Z deposition by SWR1 and therefore would be of interest to a broad readership. The manuscript would benefit from addressing previous models in the field, specifically regarding the insertion of the second dimer of H2A.Z/H2B; and the involvement of the acidic patch recognition by SWR1. These points should be addressed more directly with additional data.

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  2. Kinases in motion: impact of protein and small molecule interactions on kinase conformations

    This article has 14 authors:
    1. Valentina Kugler
    2. Selina Schwaighofer
    3. Andreas Feichtner
    4. Florian Enzler
    5. Jakob Fleischmann
    6. Sophie Strich
    7. Sarah Schwarz
    8. Rebecca Wilson
    9. Philipp Tschaikner
    10. Jakob Troppmair
    11. Veronika Sexl
    12. Pascal Meier
    13. Teresa Kaserer
    14. Eduard Stefan
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This article reports an important fluorescence-based reporter system to evaluate kinase conformations. This assay is applied to four different kinases that have very unique regulatory features, thereby indicating that the assay can be used to provide solid evidence on the conformational state of a large number of kinases. This paper will be of interest to researchers working on kinases and their conformational states.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  3. Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant

    This article has 7 authors:
    1. Patsy R. Tomlinson
    2. Rachel Knox
    3. Olga Perisic
    4. Helen C. Su
    5. Gemma V. Brierley
    6. Roger L. Williams
    7. Robert K. Semple
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The authors identify new mechanisms that link a PIK3R1 mutant to cellular signaling and division in Activated PI3 Kinase Delta Syndrom 1 and 2 (APDS1/2). The conclusion that this mutant serves as a dominant negative form of the protein, impacting PI3K complex assembly and IRS/AKT signaling, is important, and the evidence from constitutive and inducible systems in cultured cells is convincing. Nevertheless, there are several limitations relating to differences between cell lines and expression systems, as well as more global characterization of the protein interaction landscape, which would further enhance the work.

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  4. Uncovering the BIN1-SH3 interactome underpinning centronuclear myopathy

    This article has 10 authors:
    1. Boglarka Zambo
    2. Evelina Edelweiss
    3. Bastien Morlet
    4. Luc Negroni
    5. Mátyás Pajkos
    6. Zsuzsanna Dosztányi
    7. Soren Ostergaard
    8. Gilles Trave
    9. Jocelyn Laporte
    10. Gergo Gogl
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This work describes a novel and powerful affinity interactomics approach that allows investigators to identify networks of protein-protein interactions in cells. The important findings presented here describe the application of this technique to the SH3 domain of the membrane remodeling Bridging Integrator 1 (BIN1), the truncation of which leads to centronuclear myopathy. The authors present solid evidence that BIN1 SH3 engages with an unexpectedly high number of cellular proteins, many of which are linked to skeletal muscle disease, and evidence is presented to suggest that BIN1 may play a role in mitosis creating the potential for new avenues in drug development efforts. Some of the findings, however, are rather preliminary, and questions about differences in affinities between whole intact protein and fragment binding partners are not adequately discussed.

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  5. Human Pannexin 1 Channel is NOT Phosphorylated by Src Tyrosine Kinase at Tyr199 and Tyr309

    This article has 5 authors:
    1. Zheng Ruan
    2. Junuk Lee
    3. Yangyang Li
    4. Juan Du
    5. Wei Lü
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The current manuscript re-examines an established claim in the literature that human PANX-1 is regulated by Src kinase phosphorylation at two tyrosine residues, Y199 and Y309. This issue is important for our understanding of Pannexin channel regulation. The authors present an extensive series of experiments that fail to detect PANX-1 phosphorylation at these sites. Although the authors' approach is more rigorous than the previous studies, this work relies primarily on negative results that are not unambiguously definitive; the work nonetheless provides a compelling reason for the field to reexamine conclusions drawn in earlier studies.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 3 listsLatest version Latest activity
  6. Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane

    This article has 6 authors:
    1. Pragyansree Machhua
    2. Vignesh Gopalakrishnan Unnithan
    3. Yu Liu
    4. Yiping Jiang
    5. Lingfeng Zhang
    6. Zhihong Guo
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable study describes the molecular mechanism of daptomycin insertion into bacterial membranes. The authors provide solid in vitro evidence for the early events of daptomycin interaction with phospholipid headgroups and stronger, specific interaction with phosphatidylglycerol. This work will be of interest to bacterial membrane biologists and biochemists working in the antimicrobial resistance field.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  7. Structural insights in the GTP-driven monomerization and activation of a bacterial LRRK2 homologue using allosteric nanobodies

    This article has 5 authors:
    1. Christian Galicia
    2. Giambattista Guaitoli
    3. Marcus Fislage
    4. Christian J. Gloeckner
    5. Wim Versées
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      ROCO proteins are evolutionarily conserved GTPases characterized by the presence of a tandem "COR" domain, sometimes accompanied by a kinase domain as in the LRRK2 protein that is linked to neurodegeneration. Previously the authors have shown that two conformational nanobodies can be used to trap a ROCO protein CtRoco in a monomer-GTPyS-bound state. The high-resolution structural data here provides convincing insights into the active state conformation of CtRoco, an important initial advance towards a broader mechanistic understanding of these cryptic tandem-domain proteins.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  8. Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM

    This article has 7 authors:
    1. Lina Antenucci
    2. Salla Virtanen
    3. Chandan Thapa
    4. Minne Jartti
    5. Ilona Pitkänen
    6. Helena Tossavainen
    7. Perttu Permi
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript describes a valuable study aimed at identifying the substrate specificity of two cell wall hydrolases LSS and LytM in S. aureus. The authors show that LytM has a novel function of cleaving D-Ala-Gly instead of only Gly-Gly by using synthetic substrates and convincing NMR-based real-time kinetics measurements. The biological relevance of the reported results will have to be investigated in future in vivo experiments.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  9. ProteasomeID: quantitative mapping of proteasome interactomes and substrates for in vitro and in vivo studies

    This article has 12 authors:
    1. Aleksandar Bartolome
    2. Julia C. Heiby
    3. Domenico Di Fraia
    4. Ivonne Heinze
    5. Hannah Knaudt
    6. Ellen Späth
    7. Omid Omrani
    8. Alberto Minetti
    9. Maleen Hofmann
    10. Joanna M. Kirkpatrick
    11. Therese Dau
    12. Alessandro Ori
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents an important method and resource in cell lines and in mice for mass spectrometry-based identification of interactors of the proteasome, a multi-protein complex with a central role in protein turnover in almost all tissues and cell types. The method presented-including the experimental workflow and analysis pipeline, as well as the several lines of validation provided throughout, is convincing. Given the growing interest in protein aggregation and targeted protein degradation modalities, this work will be of interest to a broad spectrum of basic cell biologists and translational researchers.

    Reviewed by eLife, preLights

    This article has 5 evaluationsAppears in 4 listsLatest version Latest activity
  10. A Methylation-Phosphorylation Switch Controls EZH2 Stability and Hematopoiesis

    This article has 5 authors:
    1. Pengfei Guo
    2. Keshari Rajawasam
    3. Tiffany Trinh
    4. Hong Sun
    5. Hui Zhang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This is a fundamental study describing a novel methylation event on EZH2 that regulates EZH2 protein stability and hematopoiesis. The methodologies are sound and the conclusions are largely supported by solid data. The work will be of interest to biomedical researchers in the field of cancer epigenetics.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  11. Fitness landscape of substrate-adaptive mutations in evolved APC transporters

    This article has 5 authors:
    1. Foteini Karapanagioti
    2. Úlfur Á. Atlason
    3. Dirk J. Slotboom
    4. Bert Poolman
    5. Sebastian Obermaier
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable manuscript describes a genetic system in yeast used to find mutations in two distinct amino acid transporters that enable the cells to utilize additional amino acids as a nitrogen source. The study provides solid evidence in membrane proteins of a phenomenon that has been previously described in enzymes: that substrate specificity can be altered through the introduction of point mutations to either the ligand binding site or gating helices. This work establishes that amino acid transporters likely evolved specific functionality/specificity from an ancestral transporter that could transport most amino acids.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 3 listsLatest version Latest activity
  12. X-Ray Structure and enzymatic study of a Bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX

    This article has 10 authors:
    1. Isabelle Petit-Härtlein
    2. Annelise Vermot
    3. Michel Thépaut
    4. Anne Sophie Humm
    5. Florine Dupeux
    6. Jérôme Dupuy
    7. Vincent Chaptal
    8. José A. Marquez
    9. Susan M.E. Smith
    10. Franck Fieschi
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In this manuscript, the authors investigate the properties of prokaryotic NADPH oxidases (NOX) and discuss the implications for NOX regulation and function. The structure of the S. pneumoniae Nox protein is an important step forward in our understanding of procaryotic NOX enzymes and the characterization and interpretation are convincing. The results will be of interest to structural biologists as well as biochemists focusing on enzymatic functions.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  13. C. elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA

    This article has 7 authors:
    1. Claudia D. Consalvo
    2. Adedeji M. Aderounmu
    3. Helen M. Donelick
    4. P. Joe Aruscavage
    5. Debra M. Eckert
    6. Peter S. Shen
    7. Brenda L. Bass
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      To investigate the evolutionary relationship between the RNAi pathway and innate immunity, this study uses biochemistry and structural biology to investigate the trimeric complex of Dicer-1, DRH-1 (a RIGI homologue), and RDE-4, which exists in C. elegans. The results described include rigorous kinetic analysis of the enzymatic activity of the complex and a moderate resolution cryo-EM structure. The results are convincing and valuable to the broader understanding of the evolution of antiviral defense.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  14. Transcriptome-wide analysis of the function of Ded1 in translation preinitiation complex assembly in a reconstituted in vitro system

    This article has 6 authors:
    1. Fujun Zhou
    2. Julie M. Bocetti
    3. Meizhen Hou
    4. Daoming Qin
    5. Alan G. Hinnebusch
    6. Jon R. Lorsch
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This is an important paper as it is the first to use a reconstituted translation system to study competition among mRNAs for the initiation machinery. Understanding the principles of the biochemistry of mRNA competition for initiation factors cannot be achieved without such a system. The authors provide compelling evidence that Ded1 is required for efficient initiation in highly structured RNAs. A highly significant finding that validates the in vitro reconstituted system indeed recapitulates the effects of in-vivo perturbations of translation initiation.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  15. Acyl-CoA thioesterase-2 facilitates β-oxidation in glycolytic skeletal muscle in a lipid supply dependent manner

    This article has 13 authors:
    1. Carmen Bekeova
    2. Ji In Han
    3. Heli Xu
    4. Evan Kerr
    5. Brittney Blackburne
    6. Shannon C. Lynch
    7. Clementina Mesaros
    8. Marta Murgia
    9. Rajanikanth Vadigepalli
    10. Joris Beld
    11. Roberta Leonardi
    12. Nathaniel W. Snyder
    13. Erin L. Seifert
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents new data highlighting the importance of appropriate coenzyme A handling in the mitochondria for maintaining appropriate energy production capacity. Several findings regarding the role of a key metabolic enzyme in how skeletal muscle cells use different substrates for energy production are valuable and supported by solid evidence, but there are concerns whether the data support the conclusion that ACOT2 regulates mitochondrial matrix acyl-CoA levels in white skeletal muscle to facilitate fatty acid oxidation β-oxidation.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  16. Redox Regulation of Brain Selective Kinases BRSK1/2: Implications for Dynamic Control of the Eukaryotic AMPK family through Cys-based mechanisms

    This article has 11 authors:
    1. George N. Bendzunas
    2. Dominic P Byrne
    3. Safal Shrestha
    4. Leonard A Daly
    5. Sally O. Oswald
    6. Samiksha Katiyar
    7. Aarya Venkat
    8. Wayland Yeung
    9. Claire E Eyers
    10. Patrick A Eyers
    11. Natarajan Kannan
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study provides fundamental new knowledge into the role of reversible cysteine oxidation and reduction in protein kinase regulation. The data provide convincing evidence that intra-molecular disulfide bonds serve a repressive regulatory role in the Brain Selective Kinases (BRSK) 1 & 2; part of the as yet understudied 'dark kinome'. The findings will be of broad interest to biochemists, structural biologists, and those interested in the rationale design and development of next-generation kinase inhibitors.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  17. A mitochondrial carrier transports glycolytic intermediates to link cytosolic and mitochondrial glycolysis in the human gut parasite Blastocystis

    This article has 6 authors:
    1. Eva Pyrihová
    2. Martin S. King
    3. Alannah C. King
    4. M. Rey Toleco
    5. Mark van der Giezen
    6. Edmund R.S. Kunji
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study identifies candidate mitochondrial metabolite carriers in stramenopile protists that may allow these divergent eukaryotes to maintain a compartmentalized glycolytic pathway. This study fills a gap in our understanding of glycolysis evolution and opens avenues for drug design to combat stramenopile parasites. The evidence, based on phylogenetic analysis, thermostability shift assays, and in vitro reconstitution of transport reactions, is convincing, albeit lacking direct in vivo confirmation of the physiological function of these candidates.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  18. Structures of wild-type and a constitutively closed mutant of connexin26 shed light on channel regulation by CO 2

    This article has 5 authors:
    1. Deborah H. Brotherton
    2. Sarbjit Nijjar
    3. Christos G. Savva
    4. Nicholas Dale
    5. Alexander D. Cameron
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents valuable new structures of a carbamylation-mimetic K125E mutant of the Cx26 gap junction channel uncovering the cytoplasmic loop structure and information about the closed state of the channel. The cryo-EM maps are in high quality and serve as strong foundations for dissecting the gating mechanism by CO2. However, incomplete functional studies fall short of supporting the proposed mechanism of gap junction channel modulation through carbamylation.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 3 listsLatest version Latest activity
  19. Human DDX6 regulates translation and decay of inefficiently translated mRNAs

    This article has 3 authors:
    1. Ramona Weber
    2. Lara Wohlbold
    3. Chung-Te Chang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable study demonstrates the requirement of a DEAD-box helicase DDX6 for the cotranslational mRNA decay pathway in human cells. The authors performed a set of solid experiments, combining DDX6 KO cells with reporter assay and global analysis of mRNA stability/translation efficiency. Although some conclusions drawn by the authors need a more careful examination of alternative possibilities, this study will be of broad interest to RNA biologists working on translational control and mRNA stability.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  20. 7,8-Dihydroxyflavone is a direct inhibitor of pyridoxal phosphatase

    This article has 11 authors:
    1. Christoph Zink
    2. Linda Witzinger
    3. Angelika Keller
    4. Kerstin Hadamek
    5. Sebastian Bothe
    6. Martin Neuenschwander
    7. Carmen Villmann
    8. Jens Peter von Kries
    9. Hermann Schindelin
    10. Elisabeth Jeanclos
    11. Antje Gohla
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      Following small molecule screens, this study provides convincing evidence that 7,8 dihydroxyflavone (DHF) is a competitive inhibitor of pyridoxal phosphatase. These results are important since they offer an alternative mechanism for the effects of 7,8 dihdroxyflavone in cognitive improvement in several mouse models. This paper is also significant due to the interest in the phosphatases and neurodegeneration fields.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity