Biochemistry

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

Dissecting the phase separation and oligomerization activities of the carboxysome positioning protein McdB

1. Joseph L Basalla
2. Claudia A Mak
3. Jordan A Byrne
4. Maria Ghalmi
5. Y Hoang
6. Anthony G Vecchiarelli

• Curated by eLife

  Evaluation Summary:

  Carboxysomes enable the efficient fixation of carbon dioxide in specific bacteria. Phase separation has been invoked as a mechanism that drives the formation of carboxysomes. The current work focuses on the biophysical principles of how one of two essential specific protein components enable spatial regulation over carboxysomes. This important work highlights the connection between oligomerization via specific molecular interactions and phase separation. The work is of interest to the areas of biochemistry and carbon dioxide fixation as well as phase separation.

  (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 #3 agreed to share their name with the authors.)

Reviewed by Arcadia Science, eLife

Deep mutational scanning and machine learning reveal structural and molecular rules governing allosteric hotspots in homologous proteins

1. Megan Leander
2. Zhuang Liu
3. Qiang Cui
4. Srivatsan Raman

• Curated by eLife

  Evaluation Summary:

  This article seeks to address a key question in protein biophysics: are the amino acid positions (and mutations) that influence allostery conserved across homologs of a protein family? Or is allostery implemented by a distinct set of residues that varies amongst homologs? To address this question, the authors follow an innovative approach that combines deep mutational scanning with machine learning. Significant revisions are required to clarify whether the conclusions of the study are well-supported by the data. The work is potentially highly relevant to protein engineers and biophysicists.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Dynamic in vivo mapping of the methylproteome using a chemoenzymatic approach

1. Jonathan Farhi
2. Benjamin Emenike
3. Richard S. Lee
4. Christian M. Beusch
5. Robert B. Jones
6. Ashish K. Verma
7. Celina Y. Jones
8. Maryam Foroozani
9. Monica Reeves
10. Kirti Sad
11. Kiran K. Parwani
12. Pritha Bagchi
13. Roger B. Deal
14. David J. Katz
15. Anita H. Corbett
16. David E. Gordon
17. Monika Raj
18. Jennifer M. Spangle

Reviewed by ASAPbio crowd review

DNA passes through cohesin’s hinge as well as its Smc3–kleisin interface

1. James E Collier
2. Kim A Nasmyth

• Curated by eLife

  Evaluation Summary:

  This paper addresses the mechanism of entrapment of DNA in the cohesin SMC complex. Through a series of biochemical studies, the paper convincingly demonstrates that DNA enters cohesin rings through the hinge and SMC3/SCC1 interfaces. How such entrapment is regulated is important for different biological activities including sister chromatid cohesion and the formation of DNA loops. The paper will be of interest to researchers in SMC biology, DNA recombination and 3D genome organization.

  (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

Ligand-induced shifts in conformational ensembles that describe transcriptional activation

1. Sabab Hasan Khan
2. Sean M Braet
3. Stephen John Koehler
4. Elizabeth Elacqua
5. Ganesh Srinivasan Anand
6. C Denise Okafor

• Curated by eLife

  Evaluation Summary:

  The manuscript will be of broad interest to readers in the fields of biochemistry, structural, molecular, and evolutionary biology. It outlines a systematic approach in characterizing nuclear receptor ligands based on the conformational ensemble of the receptor, further exploring the idea that perturbation of the ensemble orchestrates function. The results from the combined use of experiments and simulation are promising, suggesting that the change in the ensemble is responsible for function.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

A specific role for importin-5 and NASP in the import and nuclear hand-off of monomeric H3

1. Alonso Javier Pardal
2. Andrew James Bowman

• Curated by eLife

  Evaluation Summary:

  This is a very fundamental study that challenges the paradigm that histones H3 and H4 are imported to the nucleus primarily as heterodimers. Instead this study provides compelling evidence that H3 and H4 are imported by importin 5 as monomers and dimerize on chaperones in the nucleus. The work is of relevance to colleagues studying nuclear import and epigenetic regulation.

  (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 name with the authors.)

Reviewed by eLife

Fip1 is a multivalent interaction scaffold for processing factors in human mRNA 3′ end biogenesis

1. Lena Maria Muckenfuss
2. Anabel Carmen Migenda Herranz
3. Franziska Maria Boneberg
4. Marcello Clerici
5. Martin Jinek

• Curated by eLife

  Evaluation Summary:

  The authors of this study characterize human Fip1, an important component of the 3' end processing machinery. They use X-ray crystallography to determine the molecular basis of the interactions between Fip1 and CPSF30 (at a 2:1 stoichiometry) and between Fip1 and CstF77 (at a 2:2 stoichiometry). Together with biochemical assays, they suggest that Fip1 may be central to regulating transitions with CPSF. The work will of relevance to colleagues interested in transcription and RNA processing.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife