Biochemistry

Butyrolactol A is a phospholipid flippase inhibitor that potentiates the bioactivity of caspofungin against resistant fungi

1. Xuefei Chen
2. H. Diessel Duan
3. Michael J. Hoy
4. Kalinka Koteva
5. Michaela Spitzer
6. Allison K. Guitor
7. Emily Puumala
8. Guanggan Hu
9. Bonnie Yiu
10. Sommer Chou
11. Zhuyun Bian
12. Amelia Bing Ya Guo
13. Sheng Sun
14. Nicole Robbins
15. Michael A. Cook
16. Ray Truant
17. Lesley T. MacNeil
18. Eric D. Brown
19. James W. Kronstad
20. Leah E. Cowen
21. Joseph Heitman
22. Huilin Li
23. Gerard D. Wright

Reviewed by PREreview

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

Hepatic HKDC1 deletion alleviates western diet-induced MASH in mice

1. Kai Xu
2. Irene Corona-Avila
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 F. Banani
9. Susana Wilson-Hawken
10. Tong Ihn Lee
11. Regina Barzilay
12. Richard A. Young

Reviewed by Arcadia Science

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

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

Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species

1. Man Zhu
2. Meng Ma
3. Lunan Luo
4. Feiyang Li
5. Jiashun Zheng
6. Yan Pan
7. Lu Yang
8. Ying Xiao
9. Ziyan Wang
10. Bo Xian
11. Yi Zheng
12. Hao Li
13. Jing Yang

• Curated by eLife

  eLife Assessment

  Building on earlier evidence that Topoisomerase 2 depletion can extend yeast lifespan, the authors present convincing data demonstrating that reduced Top2 levels confer significant longevity benefits in C. elegans and mice. They show that these benefits encompass not only extended survival but also improved healthspan and mitigation of aging phenotypes, supported by robust transcriptomic, epigenetic, and histological analyses. While the exact mechanistic underpinnings-such as the potential connection to classical aging pathways and the selective down-regulation of genes with active promoters-remain to be fully elucidated, the breadth of these important findings strongly indicates a conserved role for Top2 in aging regulation.

Reviewed by eLife

Alzheimer-mutant γ-secretase complexes stall amyloid β-peptide production

1. Parnian Arafi
2. Sujan Devkota
3. Emily Williams
4. Masato Maesako
5. Michael S Wolfe

• Curated by eLife

  eLife Assessment

  This manuscript provides fundamental studies to gain insight into the mutations in the presenilin-1 (PSEN1) gene on proteolytic processing of the amyloid precursor protein (APP). The authors provide compelling evidence using mutations in PSEN to understand what drives alternative substrate turnover with convincing data and rigorous analysis. This deep mechanistic study provides a framework towards the development of small molecule inhibitors to treat AD.

Reviewed by eLife