Biochemistry

Enzymatic protein fusions with 100% product yield

1. Adrian CD Fuchs

• Curated by eLife

  eLife Assessment

  This revision of important work is a versatile addition to the chemical protein modifications and bioconjugation toolbox in synthetic biology. The technology developed cleverly uses Connectase to irreversibly fuse proteins of interest together so they can be studied in their native context, with compelling well-controlled data showing the technique works for various protein partners. This work will help multiple fields to explore multi-function constructs in basic synthetic biology. This work will also be of interest to those studying fusion oncoproteins commonly expressed in various human pathologies.

Reviewed by eLife

Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein

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

• Curated by eLife

  eLife Assessment

  This valuable work provides solid evidence that a neuronal metallothionein, GIF/MT-3, incorporates metal-persulfide clusters. A variety of well-designed assays support the authors' hypothesis, revealing that sulfane sulfur is released from MT-3. The biological role of the persulfidated form is not yet clearly defined. There are caveats to the findings that limit the study, but the work will nevertheless prompt major follow-up work.

Reviewed by eLife

Hepatic HKDC1 Deletion Alleviates Western Diet-Induced MASH in Mice

1. Kai Xu
2. Irene Covila-Corona
3. María Dolores Frutos
4. María Ángeles Núñez-Sánchez
5. Dhruvi Makhanasa
6. Pratham Viral Shah
7. Grace Guzman
8. Bruno Ramos-Molina
9. Medha Priyadarshini
10. Md. Wasim Khan

Reviewed by PREreview, Arcadia Science

Protein codes promote selective subcellular compartmentalization

1. Henry R. Kilgore
2. Itamar Chinn
3. Peter G. Mikhael
4. Ilan Mitnikov
5. Catherine Van Dongen
6. Guy Zylberberg
7. Lena Afeyan
8. Salman Banani
9. Susana Wilson-Hawken
10. Tong Ihn Lee
11. Regina Barzilay
12. Richard A. Young

Reviewed by Arcadia Science

Dual-specific autophosphorylation of kinase IKK2 enables phosphorylation of substrate IκBα through a phosphoenzyme intermediate

1. Prateeka Borar
2. Tapan Biswas
3. Ankur Chaudhuri
4. Pallavi T Rao
5. Swasti Raychaudhuri
6. Tom Huxford
7. Saikat Chakrabarti
8. Gourisankar Ghosh
9. Smarajit Polley

• Curated by eLife

  eLife Assessment

  This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. The findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.

Reviewed by eLife

Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody

1. Joar Esteban Pinto Torres
2. Mathieu Claes
3. Rik Hendrickx
4. Meng Yuan
5. Natalia Smiejkowska
6. Pieter Van Wielendaele
7. Aysima Hacisuleyman
8. Hans De Winter
9. Serge Muyldermans
10. Paul AM Michels
11. Malcolm D Walkinshaw
12. Wim Versées
13. Guy Caljon
14. Stefan Magez
15. Yann G-J Sterckx

• Curated by eLife

  eLife Assessment

  This work presents valuable data demonstrating that a camelid single-domain antibody can selectively inhibit a key glycolytic enzyme in trypanosomes via an allosteric mechanism. The claim that this information can be exploited for the design of novel chemotherapeutics is solid but limited by the modest effects on parasite growth, as well as the lack of evidence for cellular target engagement in vivo.

Reviewed by eLife

Proximity Interactome analyses unveil novel regulators of IRE1α canonical signaling

1. Simon Le Goupil
2. Céline Philippe
3. Hadrien Laprade
4. Mathéo Lode
5. Rachel Boniface
6. Diana Pelizzari-Raymundo
7. Kurt Dejgaard
8. Gregor Jansen
9. Celia Limia
10. Claudio Hetz
11. S. Jalil Mahdizadeh
12. Luc Negroni
13. Marc Aubry
14. Jean-Ehrland Ricci
15. Leif A. Eriksson
16. Eric Chevet

Reviewed by Review Commons

Intraflagellar transport protein IFT172 contains a C-terminal ubiquitin-binding U-box-like domain involved in ciliary signaling

1. Nevin K Zacharia
2. Stefanie Kuhns
3. Niels Boegholm
4. Anni Christensen
5. Jiaolong Wang
6. Narcis A Petriman
7. Anna Lorentzen
8. Jindriska L Fialova
9. Lucie Menguy
10. Sophie Saunier
11. Soren T Christensen
12. Jens S Andersen
13. Sagar Bhogaraju
14. Esben Lorentzen

• Curated by eLife

  eLife Assessment

  This important work advances our understanding of intraflagellar transport, ciliogenesis, and ciliary-based signaling, by identifying the interactions of IFT172 with IFT-A components, ubiquitin-binding, and ubiquitination, mediated by IFT172 C-terminus and its role in ciliogenesis and ciliary signaling. The results of the structural analysis of the IFT172 C-terminus and the evidence for the interaction between IFT172 and IFT-A components are convincing. However, the analysis of ubiquitin-binding and ubiquitination mediated by IFT172 is incomplete.

Reviewed by eLife

Development of D-box peptides to inhibit the Anaphase Promoting Complex/Cyclosome

1. Rohan Eapen
2. Cynthia Okoye
3. Christopher Stubbs
4. Marianne Schimpl
5. Thomas Tischer
6. Eileen J. Fisher
7. Maria Zacharopoulou
8. Fernando Ferrer
9. David Barford
10. David Spring
11. Cath Lindon
12. Christopher Phillips
13. Laura S. Itzhaki

• Curated by eLife

  eLife Assessment

  The manuscript represents a fundamental advance in designing peptide inhibitors targeting Cdc20, a key activator and substrate-recognition subunit of the APC/C ubiquitin ligase. Supported by compelling biophysical and cellular evidence, the study lays a strong foundation for future developments in degron-based therapeutics. The unexpected findings regarding degradation efficiency highlight intriguing questions that merit further investigation. This work will interest researchers focused on peptide drug design targeting complex protein interactions.

Reviewed by eLife

Molecular determinants of Neu5Ac binding to a tripartite ATP independent periplasmic (TRAP) transporter

1. Parveen Goyal
2. KanagaVijayan Dhanabalan
3. Mariafrancesca Scalise
4. Rosmarie Friemann
5. Cesare Indiveri
6. Renwick CJ Dobson
7. Kutti R Vinothkumar
8. Subramanian Ramaswamy

• Curated by eLife

  eLife Assessment

  This valuable work provides novel insights into the substrate binding mechanism of a tripartite ATP-independent periplasmic (TRAP) transporter, which may be helpful for the development of specific inhibitors. The structural analysis is convincing, but additional work will be required to establish the transport mechanism as well as well as binding sites for all ligands. This study will be of interest to the membrane transport and bacterial biochemistry communities.

Reviewed by eLife