Biochemistry

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. Søren Tvorup 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 evidence supporting the findings is convincing. This paper will be of interest to cell biologists and biochemists, especially those working on cilia and signaling.

Reviewed by eLife

Purified zymogens reveal mechanisms of snake venom metalloproteinase auto-activation

1. Sophie Hall
2. Iara Aime Cardoso
3. Mark C Wilkinson
4. Maria Molina Carretero
5. Srikanth Lingappa
6. Bronwyn Rand
7. Dakang Shen
8. Johara Boldrini-França
9. Richard Stenner
10. Stefanie Kate Menzies
11. Georgia Balchin
12. Konrad Kamil Hus
13. Renaud Vincentelli
14. Andrew Mumford
15. Alastair Poole
16. Nicholas R Casewell
17. Imre Berger
18. Christiane Schaffitzel

• Curated by eLife

  eLife Assessment

  In this useful paper, the authors present a comprehensive method for the purification of recombinant Snake Venom Metalloproteinases (SVMPs) using the MultiBac expression system, explain the self-activation of the enzymes by Zn2+ incubation, and establish high-throughput screening (HTS) techniques. The authors addressed a key problem: producing a substantial amount of pure and enzymatically active SVMPs required for structural and functional studies. Altogether, this work builds a solid foundation for the large-scale production of active SVMPs for future biochemical and structural characterization as well as for drug discovery, albeit leaving certain caveats about the universal applicability of the described methodology for the production of any recombinant SVMPs.

Reviewed by eLife

Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period

1. Fidel Emmanuel Serrano
2. Daniela Marzoll
3. Bianca Ruppert
4. Axel CR Diernfellner
5. Michael Brunner

• Curated by eLife

  eLife Assessment

  This valuable study examines the subcellular dynamics of the mammalian circadian clock proteins PER2, CRY1, and CK1, providing solid evidence that CK1 modulates the PER2-CRY1 interaction and drives the cytoplasmic localization of PER2 complexes. This could play a key role in modulating transcriptional repression by PER2, CRY1, and CK that contributes to the molecular circadian clock. There are minor concerns regarding the overexpression of the clock proteins in this study.

  [Editors' note: this paper was previously reviewed by another journal.]

Reviewed by eLife

The structure of Egalitarian in complex with the K10 mRNA localization signal reveals a modular binding surface required for function

1. Zebin Hong
2. Li Jin
3. Jonas Mühle
4. Fulvia Bono

• Curated by eLife

  eLife Assessment

  This manuscript has convincing data that provides a high-resolution structure of the Egl-RNA complex. The findings are important to understand the formation, stability, and interactions of this complex. However, the manuscript could be improved by conducting a rigorous statistical analysis, a deeper understanding of apparent discrepancies in the stoichiometric Egl-to-RNA ratio, and exploring the specificity of this complex using a more diverse set of control RNAs.

Reviewed by eLife

Structural dynamics of IRE1 and its interaction with unfolded peptides

1. Elena Spinetti
2. Grzegorz Ścibisz
3. Gülsün Elif Karagöz
4. Roberto Covino

• Curated by eLife

  eLife Assessment

  In this important study, the authors conducted atomistic molecular dynamics simulations to probe the interactions between IRE and unfolded peptides. The results help reconcile contradicting experimental findings in the literature and offer mechanistic insights into the activation of the unfolded protein response. The atomistic molecular dynamics simulations performed are solid, leading to convincing conclusions that are partly supported by experimental validations. The use of unbiased molecular dynamics simulations, while appropriate for the current system due to its complexity, limits the time scale of events that can be observed and therefore the proposed mechanism of recognition merits further confirmation by future studies.

Reviewed by eLife

Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers

1. Xiaoyu Yu
2. Yuanjun He
3. Thedore M Kamenecka
4. Douglas J Kojetin

• Curated by eLife

  eLife Assessment

  This important study investigated whether the nuclear receptor Nur77 is regulated by a non-canonical mechanism of ligand-induced disruption of its interaction with RXRg, similar to the family member Nurr1. The overall evidence is compelling. This manuscript will be of interest to scientists focusing on mechanisms of transcriptional regulation.

Reviewed by eLife

Exogenous Amyloid Sequences: Their Role in Amyloid-Beta Heterotypic Aggregation

1. Jofre Seira Curto
2. Marina Romero Ruiz
3. Genís Pérez Collell
4. Sandra Villegas
5. Maria Rosario Fernandez
6. Natalia Sanchez de Groot

Reviewed by preLights

Distinct mechanisms of inhibition of Kv2 potassium channels by tetraethylammonium and RY785

1. Shan Zhang
2. Robyn Stix
3. Esam A Orabi
4. Nathan Bernhardt
5. José D Faraldo-Gómez

• Curated by eLife

  eLife Assessment

  This study represents an important advance in our understanding of how certain inhibitors affect the behavior of voltage gated potassium channels. Robust molecular dynamics simulation and analysis methods lead to a new proposed inhibition mechanism with convincing strength of support. This study has considerable significance for the fields of ion channel physiology and pharmacology and could aid in development of selective inhibitors for protein targets.

Reviewed by eLife

A potential anti-amyloidogenic therapy for type 2 diabetes based on the QBP1 peptide

1. María M. Tejero-Ojeda
2. Ada Bernaus Vives
3. Michal Wojciechowski
4. Dinh Quoc Huy Pham
5. Mateusz Chwastyk
6. Mario Vallejo
7. Anna Novials
8. Mariano Carrión-Vázquez

Reviewed by preLights

Membrane curvature regulates Ups1 dependent phosphatidic acid transfer across lipid bilayers

1. Fereshteh Sadeqi
2. Dexin Dong
3. Kai Stroh
4. Marian Vache
5. Jutta Metz
6. Dietmar Riedel
7. Andreas Janshoff
8. Herre Jelger Risselada
9. Caroline Kolenda
10. Michael Meinecke

• Curated by eLife

  eLife Assessment

  This fundamental study combines in vitro reconstitution experiments and molecular dynamics simulations to elucidate how membrane lipids are transported from the outer to the inner membrane of mitochondria. The authors provide convincing evidence that a positive membrane curvature is critical for membrane lipid extraction. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife