Biochemistry

Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation

1. Marco Caligaris
2. Raffaele Nicastro
3. Zehan Hu
4. Farida Tripodi
5. Johannes Erwin Hummel
6. Benjamin Pillet
7. Marie-Anne Deprez
8. Joris Winderickx
9. Sabine Rospert
10. Paola Coccetti
11. Jörn Dengjel
12. Claudio De Virgilio

• Curated by eLife

  eLife assessment

  This is an important study that shows how Snf1/AMP Kinase fine-tunes TORC1 signaling in response to glucose starvation. Their observation that Snf1 phosphorylation of the TORC regulator Pib1 and the TORC effector kinase Sch9 provides new mechanistic information on this important pathway involved in cell growth. The combination of phosphoproteomics, genetic, biochemical, and physiological experiments is generally convincing, although the results with the Pib2 SA and SE mutants are somewhat inconsistent.

Reviewed by eLife

Cryo-EM structure of the chain-elongating E3 ligase UBR5

1. Zuzana Hodáková
2. Irina Grishkovskaya
3. Hanna L. Brunner
4. Derek L. Bolhuis
5. Katarina Belačić
6. Alexander Schleiffer
7. Harald Kotisch
8. Nicholas G. Brown
9. David Haselbach

Reviewed by Review Commons

Structures of RecBCD in complex with phage-encoded inhibitor proteins reveal distinctive strategies for evasion of a bacterial immunity hub

1. Martin Wilkinson
2. Oliver J Wilkinson
3. Connie Feyerherm
4. Emma E Fletcher
5. Dale B Wigley
6. Mark S Dillingham

• Curated by eLife

  eLife assessment

  This important study addresses the ways in which bacteriophages antagonize or coopt the DNA restriction and/or recombination functions of the bacterial RecBCD helicase-nuclease. The evidence from both biochemistry and structural biology showing convergent evolution is convincing.

Reviewed by eLife

Structural basis for the Rad6 activation by the Bre1 N-terminal domain

1. Meng Shi
2. Jiaqi Zhao
3. Simin Zhang
4. Wei Huang
5. Mengfei Li
6. Xue Bai
7. Wenxue Zhang
8. Kai Zhang
9. Xuefeng Chen
10. Song Xiang

• Curated by eLife

  eLife assessment

  This fundamental study presents a crystal structure of two proteins catalyzing histone H2B ubiquitination. Findings from the structural study are further validated by mutagenesis and functional assays. This is a well-executed study providing useful information to the field.

Reviewed by eLife

Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster

1. Ahmed-Noor A Agip
2. Injae Chung
3. Alvaro Sanchez-Martinez
4. Alexander J Whitworth
5. Judy Hirst

• Curated by eLife

  eLife assessment

  This important study advances our understanding of respiratory complex I. The authors present convincing structural data for the enzyme from Drosophila melanogaster although the interpretation of conformational states is still not conclusively settled. This work will be of interest to researchers studying respiratory enzymes, the evolution of respiration, and mitochondrial diseases.

Reviewed by eLife

Nucleotide binding is the critical regulator of ABCG2 conformational transitions

1. Zsuzsanna Gyöngy
2. Gábor Mocsár
3. Éva Hegedűs
4. Thomas Stockner
5. Zsuzsanna Ritter
6. László Homolya
7. Anita Schamberger
8. Tamás I Orbán
9. Judit Remenyik
10. Gergely Szakacs
11. Katalin Goda

• Curated by eLife

  eLife assessment

  The ABC transporter ABCG2 extrudes chemotherapy reagents and other xenobiotics from a number of different tissues. How ABCG2 operates at the molecular level has been largely derived from structures and dynamics carried out in non-physiological environments. The paper presents convincing cell-based evidence describing the relationship between structural changes of ABCG2 and substrate binding using flow cytometry, confocal microscopy, and fluorescence-correlation spectroscopy methods. Both the mechanistic conclusions and methodology employed offer important insights, which will be of general interest to the biochemistry and transport biology communities.

Reviewed by eLife

Inhibition of the proton-activated chloride channel PAC by PIP2

1. Ljubica Mihaljević
2. Zheng Ruan
3. James Osei-Owusu
4. Wei Lü
5. Zhaozhu Qiu

• Curated by eLife

  eLife assessment

  Combining electrophysiology, site-directed mutagenesis, lipid pharmacology, and single particle cryo-electron microscopy, this study provides solid evidence identifying a site on the extracellular half of the transmembrane domain of Proton-Activated Chloride (PAC) channels that could be occupied by PIP2 and related lipids to promote channel desensitization. These findings are important because pharmacological information for these biologically relevant ion channels is absent.

Reviewed by eLife

Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein

1. Lauri Ilmari Aurelius Pulkkinen
2. Sarah Victoria Barrass
3. Marie Lindgren
4. Hudson Pace
5. Anna K. Överby
6. Maria Anastasina
7. Marta Bally
8. Richard Lundmark
9. Sarah Jane Butcher

Reviewed by Review Commons

Mechanism of Ca2+ transport by ferroportin

1. Jiemin Shen
2. Azaan Saalim Wilbon
3. Ming Zhou
4. Yaping Pan

• Curated by eLife

  eLife assessment

  This study makes an important contribution to the function of the iron transporter Ferroportin (Fpn). By using a combination of proteoliposome assays, mutagenesis and structural studies by cryo EM, the authors are able to demonstrate that the H+-driven transporter for Fe2+-efflux is also capable of passive Ca2+ influx. The evidence supporting the conclusions is convincing, but the rate of Ca2+ influx and the physiological relevance of Ca2+ entry is yet to be established. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife

Structures of ferroportin in complex with its specific inhibitor vamifeport

1. Elena Farah Lehmann
2. Márton Liziczai
3. Katarzyna Drożdżyk
4. Patrick Altermatt
5. Cassiano Langini
6. Vania Manolova
7. Hanna Sundstrom
8. Franz Dürrenberger
9. Raimund Dutzler
10. Cristina Manatschal

• Curated by eLife

  eLife assessment

  This important study reports cryo-EM structures of human ferroportin (FPN), a protein essential for iron transport in humans. This manuscript will be of interest to researchers studying membrane transport mechanisms as well as to those interested in drug design. The structures detail interactions between FPN and the small-molecule inhibitor vamifeport, which is currently in clinical trials for sickle cell disease, and ta new (occluded) protein conformation that is stabilized by a sybody (a nanobody selected from a synthetic library) is identified. Evidence for the mechanism of inhibition by vamifeport is convincing, but evidence for the physiological relevance of the occluded conformation is still incomplete.

Reviewed by eLife