Biochemistry

Design principles for inflammasome inhibition by pyrin-only-proteins

1. Shuai Wu
2. Archit Garg
3. Zachary Mazanek
4. Gretchen Belotte
5. Jeffery J Zhou
6. Christina M Stallings
7. Jacob Lueck
8. Aubrey Roland
9. Michael A Chattergoon
10. Jungsan Sohn

• Curated by eLife

  eLife assessment

  In this useful and potentially important manuscript, Mazanek and colleagues combine computational analysis and in vitro experiments to develop a comprehensive analysis of the ability of pyrin-only proteins (POPs) to inhibit inflammasome assembly. The results lead the authors to propose that a mixture of favorable and unfavorable interaction surfaces is required for a POP to inhibit a given inflammasome component. The results presented are solid, but additional experimentation is required to fully justify the authors' model.

Reviewed by eLife

Mitochondrial protein import clogging as a mechanism of disease

1. Liam P Coyne
2. Xiaowen Wang
3. Jiyao Song
4. Ebbing de Jong
5. Karin Schneider
6. Paul T Massa
7. Frank A Middleton
8. Thomas Becker
9. Xin Jie Chen

• Curated by eLife

  eLife assessment

  This manuscript provides valuable insight into the molecular mechanism by which destabilized mitochondrial proteins 'clog' import channels and contribute to the pathologic mitochondrial and cellular dysfunction implicated in human disease. The evidence supporting this conclusion is solid, utilizing yeast, mammalian cell culture, and mouse models. However, additional characterization of import clogging in the mammalian model systems would strengthen this study. This work will be of broad interest to researchers in the fields of mitochondrial biology, protein quality control and proteostasis.

Reviewed by eLife

Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state

1. Abhilash Padavannil
2. Anjaneyulu Murari
3. Shauna-Kay Rhooms
4. Edward Owusu-Ansah
5. James A Letts

• Curated by eLife

  eLife assessment

  This important work provides new insights into the structure and function of respiratory complex I. The cryoEM data are convincing but the assignment of different conformations of the enzyme complex to specific functional states has not yet been conclusively determined. This work will be of interest to researchers studying the molecular basis of energy metabolism, the evolution of respiratory enzyme complexes, and mitochondrial diseases.

Reviewed by eLife

High-resolution structures with bound Mn2+ and Cd2+ map the metal import pathway in an Nramp transporter

1. Shamayeeta Ray
2. Samuel P Berry
3. Eric A Wilson
4. Casey H Zhang
5. Mrinal Shekhar
6. Abhishek Singharoy
7. Rachelle Gaudet

• Curated by eLife

  eLife assessment

  This manuscript provides fundamental new insight into protein conformational transitions underlying the transport mechanism of Nramps, an important and widespread transporter family that facilitates the uptake and movement of essential transition metals. Eight new crystallographic structures of the prokaryotic homolog draNRMP in a variety of ligand-bound and conformational states, along with companion molecular dynamics simulations and metal binding and transport assays, provide compelling evidence supporting most of the conclusions. These findings will be of broad interest to scientists studying transport mechanisms and ligand recognition.

Reviewed by eLife

Peptides that Mimic RS repeats modulate phase separation of SRSF1, revealing a reliance on combined stacking and electrostatic interactions

1. Talia Fargason
2. Naiduwadura Ivon Upekala De Silva
3. Erin Powell
4. Zihan Zhang
5. Trenton Paul
6. Jamal Shariq
7. Steve Zaharias
8. Jun Zhang

• Curated by eLife

  eLife assessment

  This study convincingly demonstrates that the splicing factor SRSF1 can be solubilized in the presence of short RS or ER-containing peptides, and uses this discovery to determine the solution NMR structure of SRSF1, as well as to map its interactions with RS peptides. These findings are important in that SR proteins are key regulators of alternative splicing but their study has been greatly hampered by their low solubility. The development of a general method that allows the structural and biochemical analysis of SR proteins in solution will have broad applications.

Reviewed by eLife

In-Depth Characterization of Apoptosis N-Terminome Reveals a Link Between Caspase-3 Cleavage and Posttranslational N-Terminal Acetylation

1. Rawad Hanna
2. Andrey Rozenberg
3. Layla Saied
4. Daniel Ben-Yosef
5. Tali Lavy
6. Oded Kleifeld

Reviewed by Review Commons

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