Biochemistry

Cryo-EM structure of the endothelin-1-ETB-Gi complex

1. Fumiya K Sano
2. Hiroaki Akasaka
3. Wataru Shihoya
4. Osamu Nureki

• Curated by eLife

  eLife assessment

  Based on the Cryo-EM structure of human ETB in complex with the vasoconstricting peptide ET-1 and the inhibitory G-protein (Gi), this valuable study presents convincing data on how agonist binding is coupled to Gi-protein binding. The complex structure is solid and will appeal to the GPCR and pharmacology communities.

Reviewed by eLife

Concurrent remodelling of nucleolar 60S subunit precursors by the Rea1 ATPase and Spb4 RNA helicase

1. Valentin Mitterer
2. Matthias Thoms
3. Robert Buschauer
4. Otto Berninghausen
5. Ed Hurt
6. Roland Beckmann

• Curated by eLife

  eLife assessment

  This fundamental study substantially advances our understanding of the process of ribosome maturation. The authors have purified and determined the structures of several nucleolar ribosome assembly intermediates in yeast using cryo-electron microscopy (cryo-EM). The study combines genetic, biochemical, and structural analysis to provide compelling support for the conclusions the authors wish to draw. The work will be of broad interest to cell biologists, biochemists, and structural biologists.

Reviewed by eLife

Targeted proteomics as a tool to detect SARS-CoV-2 proteins in clinical specimens

1. Karel Bezstarosti
2. Mart M. Lamers
3. Wouter A. S. Doff
4. Peter C. Wever
5. Khoa T. D. Thai
6. Jeroen J. A. van Kampen
7. Bart L. Haagmans
8. Jeroen A. A. Demmers

Reviewed by PREreview, ScreenIT

Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15

1. Luba Mahbub
2. Guennadi Kozlov
3. Pengyu Zong
4. Emma L Lee
5. Sandra Tetteh
6. Thushara Nethramangalath
7. Caroline Knorn
8. Jianning Jiang
9. Ashkan Shahsavan
10. Lixia Yue
11. Loren Runnels
12. Kalle Gehring

• Curated by eLife

  eLife assessment

  In this potentially important study, Mahbub and colleagues examine how the small GTPase ARL15 regulates ion transport. Using a complementary array of techniques, the authors gathered solid evidence for the binding of ARL15 to CNNM proteins, resulting in a proposal how this may affect the function of the TRPM7 channel. Additional experiments are required to fully substantiate the claims.

Reviewed by eLife

Characterization of the REC114‐MEI4‐IHO1 complex regulating meiotic DNA double‐strand break formation

1. Hamida Laroussi
2. Ariadna B Juarez‐Martinez
3. Aline Le Roy
4. Elisabetta Boeri Erba
5. Frank Gabel
6. Bernard de Massy
7. Jan Kadlec

Reviewed by Review Commons

The structural basis of the multi-step allosteric activation of Aurora B kinase

1. Dario Segura-Peña
2. Oda Hovet
3. Hemanga Gogoi
4. Jennine Dawicki-McKenna
5. Stine Malene Hansen Wøien
6. Manuel Carrer
7. Ben E Black
8. Michele Cascella
9. Nikolina Sekulic

• Curated by eLife

  eLife assessment

  This important study investigates the dynamic activation mechanism of a key mitotic kinase complex, Aurora B/INCENP. The method of generating specifically phosphorylated forms of the complex is elegant, supporting a compelling biochemical analysis of how these sites synergistically activate Aurora B. However, the limitations of the molecular dynamics approach and how these models compare to previous structural studies are incompletely addressed. This work will be of interest to cell biologists and biochemists studying cell division and kinase regulation.

Reviewed by eLife

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