Biochemistry

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

Caenorhabditis elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA

1. Claudia D Consalvo
2. Adedeji M Aderounmu
3. Helen M Donelick
4. P Joseph Aruscavage
5. Debra M Eckert
6. Peter S Shen
7. Brenda L Bass

• Curated by eLife

  eLife assessment

  To investigate the evolutionary relationship between the RNAi pathway and innate immunity, this valuable 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 add to the broader understanding of the evolution of antiviral defense.

Reviewed by eLife

Giardia intestinalis deoxyadenosine kinase has a unique tetrameric structure that enables high substrate affinity and makes the parasite sensitive to deoxyadenosine analogues

1. Farahnaz Ranjbarian
2. Karim Rafie
3. Kasturika Shankar
4. Sascha Krakovka
5. Staffan G. Svärd
6. Lars-Anders Carlson
7. Anders Hofer

Reviewed by Review Commons

CK-666 and CK-869 differentially inhibit Arp2/3 iso-complexes

1. LuYan Cao
2. Shaina Huang
3. Angika Basant
4. Miroslav Mladenov
5. Michael Way

Reviewed by Review Commons

Transcriptome-wide analysis of the function of Ded1 in translation preinitiation complex assembly in a reconstituted in vitro system

1. Fujun Zhou
2. Julie M Bocetti
3. Meizhen Hou
4. Daoming Qin
5. Alan G Hinnebusch
6. Jon R Lorsch

• 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 of highly structured mRNAs. The findings are significant and validate the in vitro reconstituted system by recapitulating the effects of in-vivo perturbations of translation initiation by Ded1 mutants.

Reviewed by eLife