Biochemistry

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

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

A multi-hierarchical approach reveals d-serine as a hidden substrate of sodium-coupled monocarboxylate transporters

1. Pattama Wiriyasermkul
2. Satomi Moriyama
3. Masataka Suzuki
4. Pornparn Kongpracha
5. Nodoka Nakamae
6. Saki Takeshita
7. Yoko Tanaka
8. Akina Matsuda
9. Masaki Miyasaka
10. Kenji Hamase
11. Tomonori Kimura
12. Masashi Mita
13. Jumpei Sasabe
14. Shushi Nagamori

• Curated by eLife

  eLife assessment

  This study shows compelling evidence that the less common D-serine stereoisomer is transported in the kidney by the neutral amino acid transporter ASCT2 and that it is a non-canonical substrate for sodium-coupled monocarboxylate transporter SMCTs. With a multi-hierarchical approach, this important study further shows that Ischemia-Reperfusion Injury in the kidney causes a specific increment in renal reabsorption carried out, in part, by ASCT2.

Reviewed by eLife

Identification of an evolutionary conserved binding motif responsible for the recruitment of NMD factors to the UPF1 helicase

1. Irène Barbarin-Bocahu
2. Nathalie Ulryck
3. Amandine Rigobert
4. Nadia Ruiz Gutierrez
5. Laurence Decourty
6. Mouna Raji
7. Bhumika Garkhal
8. Hervé Le Hir
9. Cosmin Saveanu
10. Marc Graille

Reviewed by Review Commons