Biochemistry

7,8-Dihydroxyflavone is a direct inhibitor of human and murine pyridoxal phosphatase

1. Marian Brenner
2. Christoph Zink
3. Linda Witzinger
4. Angelika Keller
5. Kerstin Hadamek
6. Sebastian Bothe
7. Martin Neuenschwander
8. Carmen Villmann
9. Jens Peter von Kries
10. Hermann Schindelin
11. Elisabeth Jeanclos
12. Antje Gohla

• 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

Human pannexin 1 channel is not phosphorylated by Src tyrosine kinase at Tyr199 and Tyr309

1. Zheng Ruan
2. Junuk Lee
3. Yangyang Li
4. Juan Du
5. Wei Lü

• 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

Redox regulation and dynamic control of brain-selective kinases BRSK1/2 in the AMPK family through cysteine-based mechanisms

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

• 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 rational design and development of next-generation kinase inhibitors.

Reviewed by eLife

Quantitative mapping of proteasome interactomes and substrates using ProteasomeID

1. Aleksandar Bartolome
2. Julia C Heiby
3. Domenico Di Fraia
4. Ivonne Heinze
5. Hannah Knaudt
6. Ellen Spaeth
7. Omid Omrani
8. Alberto Minetti
9. Maleen Hofmann
10. Joanna M Kirkpatrick
11. Therese Dau
12. Alessandro Ori

• 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

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

1. Alexander S Baier
2. Nathan Gioacchini
3. Priit Eek
4. Erik M Leith
5. Song Tan
6. Craig L Peterson

• 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.

Reviewed by eLife

Divergent folding-mediated epistasis among unstable membrane protein variants

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

• Curated by eLife

  eLife assessment

  This important study describes exhaustive deep mutational scanning (DMS) of the gonadotropin-releasing hormone wild-type receptor and for two single point mutations that impact its folding and structure, monitoring how plasma membrane expression levels are influenced by the introduced mutations. With solid evidence, the authors have pioneered an exploration of the interaction between mutations (epistasis) in a membrane protein, with a potential for explaining membrane protein evolution and genetic diseases.

Reviewed by eLife

A mitochondrial carrier transports glycolytic intermediates to link cytosolic and mitochondrial glycolysis in the human gut parasite Blastocystis

1. Eva Pyrihová
2. Martin S King
3. Alannah C King
4. M Rey Toleco
5. Mark van der Giezen
6. Edmund RS Kunji

• 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

Nuclear Receptor Interdomain Communication is Mediated by the Hinge with Ligand Specificity

1. Saurov Hazarika
2. Tracy Yu
3. Arumay Biswas
4. Namita Dube
5. Priscilla Villalona
6. C. Denise Okafor

Reviewed by Arcadia Science

Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b

1. Ivana Vukovic
2. Samantha M Barnada
3. Jonathan W Ruffin
4. Jon Karlin
5. Ravi Kumar Lokareddy
6. Gino Cingolani
7. Steven B McMahon

Reviewed by Review Commons

Structures of wild-type and a constitutively closed mutant of connexin26 shed light on channel regulation by CO2

1. Deborah H Brotherton
2. Sarbjit Nijjar
3. Christos G Savva
4. Nicholas Dale
5. Alexander David Cameron

• 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, providing convincing evidence in support of a mechanism where CO2-mediated carbamylation of Lys125 shifts the conformational equilibrium towards a state where the N-terminus occludes the pore of the channel. This information will be of interest to biochemists, cell biologists and biophysicists interested in the function of gap-junction channels in health and disease.

Reviewed by eLife