Biochemistry

An auto-inhibited state of protein kinase G and implications for selective activation

1. Rajesh Sharma
2. Jeong Joo Kim
3. Liying Qin
4. Philipp Henning
5. Madoka Akimoto
6. Bryan VanSchouwen
7. Gundeep Kaur
8. Banumathi Sankaran
9. Kevin R MacKenzie
10. Giuseppe Melacini
11. Darren E Casteel
12. Friedrich W Herberg
13. Choel Kim

• Curated by eLife

  Evaluation Summary:

  This reported crystal structure of nearly-full-length cGMP-dependent protein kinase β (PGK1β) provides new insights into how the activity of the PKG catalytic domain is held in check by intramolecular interactions between both the upstream regulatory cGMP-binding domains and the autoinhibitory segment and the catalytic domain, and how cGMP binding to the cGMP-binding domains can relieve these inhibitory constraints leading to an increase in catalytic activity. The structure of the activating PKGIα R177Q CNB-A domain mutant, which resembles a cGMP-bound wild type CNB-A domain, provides a nice explanation for how this point mutation activates PKG Iα and leads to the development of the TAAD (Thoracic Aortic Aneurysms and Dissections) syndrome. The work will be of specific interest to the cyclic nucleotide community, and to the broader signaling community in general.

  (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 #2 agreed to share their names with the authors.)

Reviewed by eLife

PH domain-mediated autoinhibition and oncogenic activation of Akt

1. Hwan Bae
2. Thibault Viennet
3. Eunyoung Park
4. Nam Chu
5. Antonieta Salguero
6. Michael J Eck
7. Haribabu Arthanari
8. Philip A Cole

• Curated by eLife

  Evaluation Summary:

  Bae et al. examine the regulatory role of the PH domain of the AKT Ser/ Thr kinase, finding a key set of interactions that mediate autoinhibitory interactions between PH and kinase domains. The work provides additional mechanistic understanding of the E17K mutation, a common variant in human cancers. This manuscript will be of great interest to scientists focused on protein kinase regulation and molecular mechanisms that control signal transduction.

  (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

Glutamine metabolism modulates chondrocyte inflammatory response

1. Manoj Arra
2. Gaurav Swarnkar
3. Naga Suresh Adapala
4. Syeda Kanwal Naqvi
5. Lei Cai
6. Muhammad Farooq Rai
7. Srikanth Singamaneni
8. Gabriel Mbalaviele
9. Robert Brophy
10. Yousef Abu-Amer

• Curated by eLife

  Evaluation Summary:

  This manuscript focuses on identifying how metabolism can influence the response of cartilage cells to inflammation. This has relevance to the painful disease known as osteoarthritis. Modulation of cell metabolism in the right direction can serve to protect joint cartilage from the negative effects of inflammation which causes onset and disease progression.

  (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

Fusion with heat-resistant obscure (Hero) proteins have the potential to improve the molecular property of recombinant proteins

1. Eri Morimoto
2. Kotaro Tsuboyama
3. Yukihide Tomari

Reviewed by ASAPbio crowd review

Translational Activity Controls Ribophagic Flux and Turnover of Distinct Ribosome Pools

1. Jakob Trendel
2. Milan Aleksić
3. Matilde Bertolini
4. Marco Jochem
5. Günter Kramer
6. Stefan Pfeffer
7. Bernd Bukau
8. Jeroen Krijgsveld

Reviewed by ASAPbio crowd review

Increasing protein stability by inferring substitution effects from high-throughput experiments

1. Rasmus Krogh Norrild
2. Kristoffer Enøe Johansson
3. Charlotte O’Shea
4. Jens Preben Morth
5. Kresten Lindorff-Larsen
6. Jakob Rahr Winther

Reviewed by ASAPbio crowd review

Double NPY motifs at the N-terminus of the yeast t-SNARE Sso2 synergistically bind Sec3 to promote membrane fusion

1. Maximilian Peer
2. Hua Yuan
3. Yubo Zhang
4. Katharina Korbula
5. Peter Novick
6. Gang Dong

Reviewed by Review Commons

Specific binding of Hsp27 and phosphorylated Tau mitigates abnormal Tau aggregation-induced pathology

1. Shengnan Zhang
2. Yi Zhu
3. Jinxia Lu
4. Zhenying Liu
5. Amanda G Lobato
6. Wen Zeng
7. Jiaqi Liu
8. Jiali Qiang
9. Shuyi Zeng
10. Yaoyang Zhang
11. Cong Liu
12. Jun Liu
13. Zhuohao He
14. R Grace Zhai
15. Dan Li

• Curated by eLife

  Evaluation Summary:

  The authors found elevated Hsp 27 levels in brains from Alzheimer disease patients. Hsp27 co-localized with p-Tau, efficiently prevented pTau fibrillation in vitro, and mitigated neuropathology of pTau aggregation in a Drosophila tauopathy model. A series of biochemical assays is presented to supporrt the claim that Hsp27 prevents abnormal Tau aggregation and p-Tau pathology. Overall, the study is well designed and presented, and the data convincingly support this major conclusion, which is relevant to colleagues studying neurodegeneration.

  (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

Structural and biochemical basis of interdependent FANCI‐FANCD2 ubiquitination

1. Kimon Lemonidis
2. Martin L Rennie
3. Connor Arkinson
4. Viduth K Chaugule
5. Mairi Clarke
6. James Streetley
7. Helen Walden

Reviewed by Review Commons

Selenocyanate derived Se-incorporation into the nitrogenase Fe protein cluster

1. Trixia M Buscagan
2. Jens T Kaiser
3. Douglas C Rees

• Curated by eLife

  Evaluation Summary:

  This manuscript describes the unexpected observation of selenium exchange into an iron-sulfur cluster cofactor of a component of nitrogenase. The work sets the stage for future mechanistic study of this phenomenon. It also provides a roadmap for the study of sulfide exchange in other classes of iron-sulfur cluster 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife