Biochemistry

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 D 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 Baranda
3. Jonathan W. Ruffin
4. Jon Karlin
5. Steven B. McMahon

Reviewed by Review Commons

The co-receptor Tspan12 directly captures Norrin to promote ligand-specific β-catenin signaling

1. Elise S. Bruguera
2. Jacob P. Mahoney
3. William I. Weis

• Curated by eLife

  eLife assessment

  This is a fundamental study that addresses the key question of how the tetraspanin Tspan12 functions biochemically as a co-receptor for Norrin to initiate β-catenin signaling. The strength of the work lies in the rigorous and compelling binding analyses involving various purified receptors, co-receptors, and ligands, as well as molecular modeling by AlphaFold that was subsequently validated by an extensive series of mutagenesis experiments. The study advances the field by providing a novel mechanism of co-receptor function and shedding new light on how signaling specificity is achieved in the complex Wnt/Norrin signaling system.

Reviewed by eLife

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

Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus

1. Natalia E Ketaren
2. Fred D Mast
3. Peter C Fridy
4. Jean Paul Olivier
5. Tanmoy Sanyal
6. Andrej Sali
7. Brian T Chait
8. Michael P Rout
9. John D Aitchison

• Curated by eLife

  eLife assessment

  This study presents important insights on the impact of SARS-CoV-2 variants on the binding and neutralization of a small library of nanobodies. The authors should be applauded for their comprehensive in vitro and in silico analyses of nanobody targeting of SARS-CoV-2 variants. The evidence supporting the claims of the authors is now convincing. This work will be of great interest to researchers in the fields of antibody/nanobody engineering and SARS-CoV-2 therapeutics.

Reviewed by eLife

Structural insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies

1. Christian Galicia
2. Giambattista Guaitoli
3. Marcus Fislage
4. Christian Johannes Gloeckner
5. Wim Versées

• Curated by eLife

  eLife assessment

  The fundamental study by Galicia C. et al. captured the GTP-bound active structure of CtRoco, a homolog of human LRRK2, using conformation-specific nanobodies. This convincing body of work reports the first structure of a GTP-bound ROCO protein, illustrating how GTP facilitates the dimer-to-monomer transition of CtRoco and functional activation.

Reviewed by eLife