Biochemistry

ATP-competitive and allosteric inhibitors induce differential conformational changes at the autoinhibitory interface of Akt

1. Alexandria L Shaw
2. Matthew AH Parson
3. Linda Truebestein
4. Meredith L Jenkins
5. Thomas A Leonard
6. John E Burke

Reviewed by ASAPbio crowd review

MitoStores: chaperone‐controlled protein granules store mitochondrial precursors in the cytosol

1. Lena Krämer
2. Niko Dalheimer
3. Markus Räschle
4. Zuzana Storchová
5. Jan Pielage
6. Felix Boos
7. Johannes M Herrmann

Reviewed by ASAPbio crowd review

Tuning aromatic contributions by site-specific encoding of fluorinated phenylalanine residues in bacterial and mammalian cells

1. Grace D. Galles
2. Daniel T. Infield
3. Colin J. Clark
4. Marcus L. Hemshorn
5. Shivani Manikandan
6. Frederico Fazan
7. Ali Rasouli
8. Emad Tajkhorshid
9. Jason D. Galpin
10. Richard B. Cooley
11. Ryan A. Mehl
12. Christopher A. Ahern

• Curated by Biophysics Colab

  Endorsement statement (3 October 2022)

  The preprint by Galles et al. reports the generation of pyrrolysine-based aminoacyl-tRNA synthetases capable of incorporating fluorinated phenylalanine non-canonical amino acids into proteins expressed in either bacteria or mammalian cells. For the most extensively characterized synthetases, fluorinated phenylalanine derivatives were successfully incorporated into GFP and two membrane proteins (CFTR and Nav1.5) at expression levels adequate for biochemical studies, suggesting that the approach could be combined with multiple different structural and biophysical techniques. The work provides a valuable tool that will enable the functional role of cation-pi interactions to be interrogated in both soluble and integral membrane proteins.

  (This endorsement by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

Reviewed by Biophysics Colab

Adiponectin reverses β‐Cell damage and impaired insulin secretion induced by obesity

1. Ana Cláudia Munhoz
2. Julian D. C. Serna
3. Eloisa Aparecida Vilas‐Boas
4. Camille C. Caldeira da Silva
5. Tiago G. Santos
6. Francielle C. Mosele
7. Sergio L. Felisbino
8. Vilma Regina Martins
9. Alicia J. Kowaltowski

Reviewed by ASAPbio crowd review

Structural basis of Yta7 ATPase-mediated nucleosome disassembly

1. Feng Wang
2. Xiang Feng
3. Qing He
4. Hua Li
5. Huilin Li

• Curated by eLife

  eLife Assessment:

  This manuscript presents the cryo-EM structure of the Yta7 chromatin remodeler, which provides new mechanistic insight into how this AAA+ protein unfolds histone H3 in yeast for DNA replication. The study details the putative role of the C-terminal bromodomains, as well as an N-terminal bromo-interaction motif, in engaging nucleosomes for subsequent capture of the H3 tail for ATP-driven translocation by the upper AAA1 ring. The accompanying functional work helps establish the proposed nucleosome recognition mechanism, providing a structural framework that may be generally used by AAA+ nucleosome remodelers. The work will be of interest to colleagues in chromatin biology as well as all who study the very large family of AAA-ATPases.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes

1. Manuel F Juette
2. Jordan D Carelli
3. Emily J Rundlet
4. Alan Brown
5. Sichen Shao
6. Angelica Ferguson
7. Michael R Wasserman
8. Mikael Holm
9. Jack Taunton
10. Scott C Blanchard

• Curated by eLife

  eLife Assessment:

  Juette and coworkers employed single-molecule fluorescence, cryogenic-electron microscopy structures, and in vivo measurements to investigate the mechanism whereby two natural products with potential as cancer therapeutics, didemnin B and ternatin-4, act. The compounds are shown to inhibit tRNA accommodation within the ribosomal A site during translation elongation by interfering with movement of eukaryotic elongation factor 1 alpha after its activation by the GTPase activation site of the ribosome, with the degree and nature of this restriction differing subtly between the two compounds, leading to more marked differences in their effects on global translation and cell growth. The compelling results of this interdisciplinary work solidify prior conclusions, particularly on didemnin B, and illuminate the similarities and differences on how these two drugs interfere with the normal functioning of the elongating ribosome in vitro and inhibit protein synthesis and cell growth in vivo. Some revisions of figures and text are required to clarify the results and the authors' interpretations.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

A novel fold for acyltransferase-3 (AT3) proteins provides a framework for transmembrane acyl-group transfer

1. Kahlan E Newman
2. Sarah N Tindall
3. Sophie L Mader
4. Syma Khalid
5. Gavin H Thomas
6. Marjan W Van Der Woude

• Curated by eLife

  Evaluation Summary:

  By integrating a range of computational techniques, the authors generated a structural model for the AT3 domain, which is predicted to adopt a new fold. The key features of the structural model are consistent with the activity of the enzyme as an acyltransferase, with a transmembrane channel that can accommodate an acyl-CoA donor, and an outer cavity formed with a second domain that can accommodate a nascent LPS molecule as substrate. Overall, the study will help stimulate specific experimental analyses that can further evaluate and improve the model for better mechanistic understanding of this class of enzymes. The work will be of interest to structural biologists, and all studying acyltransferase enzymes.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

High-throughput proteomics of nanogram-scale samples with Zeno SWATH MS

1. Ziyue Wang
2. Michael Mülleder
3. Ihor Batruch
4. Anjali Chelur
5. Kathrin Textoris-Taube
6. Torsten Schwecke
7. Johannes Hartl
8. Jason Causon
9. Jose Castro-Perez
10. Vadim Demichev
11. Stephen Tate
12. Markus Ralser

Reviewed by Review Commons

Hypoxia causes pancreatic β-cell dysfunction by activating a transcriptional repressor BHLHE40

1. Tomonori Tsuyama
2. Yoshifumi Sato
3. Tatsuya Yoshizawa
4. Takaaki Matsuoka
5. Kazuya Yamagata

Reviewed by Review Commons

Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control

1. Meiling Wu
2. Anda Zhao
3. Xingchen Yan
4. Hongyang Gao
5. Chunwang Zhang
6. Xiaomin Liu
7. Qiwen Luo
8. Feizhou Xie
9. Shanlin Liu
10. Dongyun Shi

• Curated by eLife

  Evaluation Summary:

  There is a debate whether ROS (reactive oxygen species) generated through redox signaling could be a friend or foe. There are several paradoxical studies (both animal and human) wherein exercise health benefits were reported to be accompanied by increases in ROS generation. Utilizing the in-vitro studies as well as mice model work, this manuscript illustrates the different regulatory mechanisms of exercise and antioxidant intervention on redox balance and blood glucose level in diabetes. The manuscript does address some advancements in the area of research specialization.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife