Showing page 2 of 14 pages of list content

  1. 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
  2. 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
  3. 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
  4. Structural and dynamic changes in P-Rex1 upon activation by PIP 3 and inhibition by IP 4

    This article has 8 authors:
    1. Sandeep K. Ravala
    2. Sendi Rafael Adame-Garcia
    3. Sheng Li
    4. Chun-Liang Chen
    5. Michael A. Cianfrocco
    6. J. Silvio Gutkind
    7. Jennifer N. Cash
    8. John J. G. Tesmer
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study contributes insights into the regulatory mechanisms of a protein governing cell migration at the membrane. The integration of approaches revealing protein structure and dynamics provides convincing data for a model of regulation and suggests a new allosteric role for a solubilized phospholipid headgroup. The work will be interesting to researchers focusing on signaling mechanisms, cell motility, and cancer metathesis.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  5. The non–muscle actinopathy–associated mutation E334Q in cytoskeletal γ– actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins

    This article has 8 authors:
    1. Johannes N. Greve
    2. Anja Marquardt
    3. Robin Heiringhoff
    4. Theresia Reindl
    5. Claudia Thiel
    6. Nataliya Di Donato
    7. Manuel H. Taft
    8. Dietmar J. Manstein
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents a valuable characterization of the biochemical consequences of a disease-associated point mutation in a nonmuscle actin. The study uses well-characterized in vitro assays to explore function. The data are convincing and should be helpful to others.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 2 listsLatest version Latest activity
  6. Divergent Folding-Mediated Epistasis Among Unstable Membrane Protein Variants

    This article has 10 authors:
    1. Laura M. Chamness
    2. Charles P. Kuntz
    3. Andrew G. McKee
    4. Wesley D. Penn
    5. Christopher M. Hemmerich
    6. Douglas B. Rusch
    7. Hope Woods
    8. Dyotima
    9. Jens Meiler
    10. Jonathan P. Schlebach
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The important study describes exhaustive deep mutational scanning (DMS) of the gonadotropin-releasing hormone wild-type receptor and for two single point mutations reported to impact its folding and structure, monitoring how plasma membrane expression levels are affected by mutations. This important work is pioneering in exploring the interaction between mutations (epistasis) in a membrane protein, with a potential for explaining membrane protein evolution and genetic diseases. The evidence provided for some mutations is convincing, but it remains incomplete and harder to interpret for others without further validation of folding and stability properties of the mutants.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 3 listsLatest version Latest activity
  7. Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein

    This article has 13 authors:
    1. Yasuhiro Shinkai
    2. Yunjie Ding
    3. Toru Matsui
    4. George Devitt
    5. Masahiro Akiyama
    6. Tang-Long Shen
    7. Motohiro Nishida
    8. Tomoaki Ida
    9. Takaaki Akaike
    10. Sumeet Mahajan
    11. Jon M. Fukuto
    12. Yasuteru Shigeta
    13. Yoshito Kumagai
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study provides useful evidence that GIF/MT-3 harbors sulfane sulfur, which may play a role in zinc coordination. The study includes a variety of well-designed assays to support the authors' hypothesis, revealing that sulfane sulfur is released from MT-3. The analysis and conclusions could benefit from a more rigorous approach to analyzing sulfur and zinc content in recombinant MT3 protein, leaving the evidence in parts incomplete.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  8. The catalytic mechanism of the RNA methyltransferase METTL3

    This article has 12 authors:
    1. Ivan Corbeski
    2. Pablo Andrés Vargas-Rosales
    3. Rajiv Kumar Bedi
    4. Jiahua Deng
    5. Dylan Coelho
    6. Emmanuelle Braud
    7. Laura Iannazzo
    8. Yaozong Li
    9. Danzhi Huang
    10. Mélanie Ethève-Quelquejeu
    11. Qiang Cui
    12. Amedeo Caflisch
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study combines experimental and computational data to address crucial aspects of RNA methylation by a vital RNA methyltransferase (MTase). The authors have provided compelling, strong evidence, utilizing well-established techniques, to elucidate aspects of the methyl transfer mechanism of methyltransferase-like protein 3 (METTL3), which is a part of the METTL3-14 complex. This work will be of broad interest to biochemists, biophysicists, and cell biologists alike.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  9. ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6 specific nanobody restricts M. tuberculosis growth in macrophages

    This article has 14 authors:
    1. Timothy A Bates
    2. Mila Trank-Greene
    3. Xammy Nguyenla
    4. Aidan Anastas
    5. Ilaria R Merutka
    6. Shandee D Dixon
    7. Anthony Shumate
    8. Abigail R Groncki
    9. Matthew AH Parson
    10. Eric Barklis
    11. John E Burke
    12. Ujwal Shinde
    13. Hidde L Ploegh
    14. Fikadu G Tafesse
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful study investigates two secreted Mycobacterium tuberculosis proteins, ESAT-6 and CFP10, using biochemical assays, including a Biolayer Interferometry assay. Solid experimental evidence demonstrates that ESAT-6 forms a tight interaction with CFP10 as a heterodimer at neutral pH and that ESAT-6 also forms a homodimer at acidic pH. Additional, more definitive evidence is required to describe how these proteins disrupt the phagosomal membrane.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  10. Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase dependent mechanism

    This article has 7 authors:
    1. Bernd K. Gilsbach
    2. Franz Y. Ho
    3. Benjamin Riebenbauer
    4. Xiaojuan Zhang
    5. Giambattista Guaitoli
    6. Arjan Kortholt
    7. Christian Johannes Gloeckner
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable manuscript reports on the relationship between GTP hydrolysis parameters and kinase activity of LRRK2, which is associated with Parkinson's disease. The authors provide a detailed accounting of the catalytic efficiency of the ROC GTPase domain of pathogenic variants of LRRK2, in comparison with the wild-type enzyme. The authors propose that phosphorylation of T1343 inhibits kinase activity and influences monomer-dimer transitions, but the experimental evidence is currently incomplete.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  11. Structural dynamics of the active HER4 and HER2/HER4 complexes is finely tuned by different growth factors and glycosylation

    This article has 5 authors:
    1. Raphael Trenker
    2. Devan Diwanji
    3. Tanner Bingham
    4. Kliment A. Verba
    5. Natalia Jura
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript describes structures of HER4 homo- and HER4/HER2 hetero-dimer complexes using single particle cryo-EM. This important work describes convincingly new structural details of these complexes that expand our understanding of their function. This work will be of interest to researchers working on cell surface signalling and kinase activity.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 2 listsLatest version Latest activity
  12. Structure-guided mutagenesis of OSCAs reveals differential activation to mechanical stimuli

    This article has 4 authors:
    1. Sebastian Jojoa-Cruz
    2. Adrienne E. Dubin
    3. Wen-Hsin Lee
    4. Andrew Ward
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The manuscript seeks to dissect the molecular underpinnings of poke and stretch activation in OSCA channels. While the structural and functional experiments are well done, and the authors present some important data, the reviewers identified weaknesses in experimental design and interpretation that render the data incomplete in supporting some of the main conclusions of the paper. Nevertheless, this work will be of interest to those working in the fields of mechanosensation, sensory biology, and ion channels.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 3 listsLatest version Latest activity
  13. Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling

    This article has 5 authors:
    1. Henning Mühlenbeck
    2. Yuko Tsutsui
    3. Mark A. Lemmon
    4. Kyle W. Bender
    5. Cyril Zipfel
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript reports important in vitro biochemical and in planta experiments to study the receptor activation mechanism of plant membrane receptor kinase complexes with non-catalytic intracellular kinase domains. Several lines of evidence convincingly show that one such putative pseudokinase, the immune receptor EFR achieves an active conformation following phosphorylation by a co-receptor kinase, and then in turn activates the co-receptor kinase allosterically to enable it to phosphorylate down-stream signaling components. This manuscript will be of interest to scientists focusing on cell signalling and allosteric regulation.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  14. Phosphorylation, disorder, and phase separation govern the behavior of Frequency in the fungal circadian clock

    This article has 7 authors:
    1. Daniyal Tariq
    2. Nicole Maurici
    3. Bradley M. Bartholomai
    4. Siddarth Chandrasekaran
    5. Jay C. Dunlap
    6. Alaji Bah
    7. Brian R. Crane
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript is a fundamental contribution to the understanding of the role of intrinsically disordered proteins in circadian clocks and the potential involvement of phase separation mechanisms. The authors convincingly report on the structural and biochemical aspects and the molecular interactions of the intrinsically disordered protein FRQ. The paper will be of interest to scientists focusing on circadian clock regulation, liquid-liquid phase separation, and phosphorylation.

    Reviewed by eLife

    This article has 10 evaluationsAppears in 2 listsLatest version Latest activity
  15. Mapping the architecture of the initiating phosphoglycosyl transferase from S. enterica O-antigen biosynthesis in a liponanoparticle

    This article has 6 authors:
    1. Greg J Dodge
    2. Alyssa J Anderson
    3. Yi He
    4. Weijing Liu
    5. Rosa Viner
    6. Barbara Imperiali
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment:

      This valuable manuscript provides solid methodologies for utilizing SMALP nanodisks for oligomer characterization. The authors present a platform for capturing and studying native membrane protein oligomerization and subsequent cryoEM analysis. The specific application of the method to WbaP, a membrane-bound phosphoglycosyl transferase, adds to our understanding of glycoconjugate production in bacteria. This manuscript would be of interest to those focusing on native membrane protein studies and antimicrobial resistance.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  16. Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens

    This article has 9 authors:
    1. Veronica Ober
    2. George B. Githure
    3. Yuri Volpato Santos
    4. Sidney Becker
    5. Gabriel Moya
    6. Jerôme Basquin
    7. Frank Schwede
    8. Esben Lorentzen
    9. Michael Boshart
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This landmark study sheds light on a long-standing puzzle in Protein kinase A activation in Trypanosoma. Extensive experimental work provides exceptional evidence for the conclusions of the work, which represents a significant advancement in our understanding of the molecular mechanism of cyclic nucleotide binding domains. The work is relevant for researchers with interests in kinases and their mechanistic study.

    Reviewed by eLife

    This article has 8 evaluationsAppears in 2 listsLatest version Latest activity
  17. Recognition of the Nucleotide-Dependent Feature Facilitates the Microtubule End-Binding of MCAK

    This article has 4 authors:
    1. Wei Chen
    2. Yin-Long Song
    3. Jian-Feng He
    4. Xin Liang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This work presents valuable new information on the microtubule-binding mode of the microtubule kinesin-13, MCAK. The authors use quantitative single-molecule studies to propose that MCAK preferentially binds to a GDP-Pi-tubulin portion of the microtubule end. However, the evidence provided to support this claim remains incomplete and would benefit from a more rigorous methodology. Additionally, the physiological relevance of the proposed binding mode remains speculative.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  18. The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase

    This article has 10 authors:
    1. Valentin Bohl
    2. Nele Merret Hollmann
    3. Tobias Melzer
    4. Panagiotis Katikaridis
    5. Lena Meins
    6. Bernd Simon
    7. Dirk Flemming
    8. Irmgard Sinning
    9. Janosch Hennig
    10. Axel Mogk
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important manuscript details the characterization of ClpL from L. monocytogenes as an effective and autonomous AAA+ disaggregase that provides enhanced heat resistance to this food-borne pathogen. The authors convincingly demonstrate that ClpL has DnaK-independent disaggregase activity towards a variety of aggregated model substrates, which is more potent than that observed with the endogenous canonical DnaK/ClpB bi-chaperone system. The work will be of broad interest to microbiologists and biochemists.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  19. A robust method for measuring aminoacylation through tRNA-Seq

    This article has 2 authors:
    1. Kristian Davidsen
    2. Lucas B Sullivan
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This valuable paper presents a new protocol for quantifying tRNA aminoacylation levels by deep sequencing. The improved methods for discrimination of aminoacyl-tRNAs from non-acylated tRNAs, more efficient splint-assisted ligation to modify the tRNAs' ends for the following RT-PCR reaction, and the use of an error-tolerating mapping algorithm to map the tRNA sequencing reads provide new tools for anyone interested in tRNA concentrations and functional states in different cells and organisms. The results and conclusions are solid with well-designed tests to optimize the protocol under different conditions.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  20. Structure and evolution of Alanine/Serine Decarboxylases and the engineering of theanine production

    This article has 7 authors:
    1. Hao Wang
    2. Biying Zhu
    3. Siming Qiao
    4. Chunxia Dong
    5. Xiaochun Wan
    6. Weimin Gong
    7. Zhaoliang Zhang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study reports biochemical and structural analysis of two PLP decarboxylase enzymes from plants. The findings are useful due to the utility of these enzymes in industrial theanine production. While certain aspects of the study are solid, other components elucidating the role of a Zn(II)-binding motif are incomplete. In addition, some of the finding could be presented more clearly, including the connections between the structural findings and the reaction mechanism. The work will be of interest to enzymologists studying PLP enzymes and those interested in enzyme engineering in plants.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity