Biochemistry

Assembly of higher-order SMN oligomers is essential for metazoan viability and requires an exposed structural motif present in the YG zipper dimer

1. Kushol Gupta
2. Ying Wen
3. Nisha S. Ninan
4. Amanda C. Raimer
5. Robert Sharp
6. Ashlyn M. Spring
7. Kathryn L. Sarachan
8. Meghan C. Johnson
9. Gregory D. Van Duyne
10. A. Gregory Matera

• Curated by eLife

  Summary:

  The manuscript describes a very detailed mutagenesis analysis of the dimerization / oligomerization behavior of the protein Survival Motor Neuron. Mutations in this protein cause Spinal Muscular Atrophy. Analysis of disease causing mutations show a correlation with their impact on oligomerization. A structural model that includes different domains of the protein involved in oligomerization is built from these analyses.

  This analysis is an excellent source for researchers working in the field of SMN proteins. A mechanistic interpretation of how changes in the oligomerization lead to the disease or impact the formation of membraneless organelles, is however missing. Thus, the manuscript provides an enormous amount of important mutational analysis data but does not lead to a significant advancement in our understanding of the disease mechanism.

  (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

SARS-CoV-2 beta variant substitutions alter spike glycoprotein receptor binding domain structure and stability

1. Daniel L. Moss
2. Jay Rappaport

Reviewed by ScreenIT

Impacts on the structure-function relationship of SARS-CoV-2 spike by B.1.1.7 mutations

1. Tzu-Jing Yang
2. Pei-Yu Yu
3. Yuan-Chih Chang
4. Kang-Hao Liang
5. Hsian-Cheng Tso
6. Meng-Ru Ho
7. Wan-Yu Chen
8. Hsiu-Ting Lin
9. Han-Chung Wu
10. Shang-Te Danny Hsu

Reviewed by ScreenIT

AKAP79 enables calcineurin to directly suppress protein kinase A activity

1. Timothy W Church
2. Parul Tewatia
3. Saad Hannan
4. João Antunes
5. Olivia Eriksson
6. Trevor G Smart
7. Jeanette Hellgren Kotaleski
8. Matthew G Gold

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to neuroscientists as well as a broad audience of cell biologists, as it provides new insight into the myriad of cellular functions regulated by the well-studied cAMP-dependent protein kinase, PKA. Rigorous biochemical data supports a model for PKA inactivation wherein dephosphorylation of the PKA regulatory subunit within a multiprotein complex leads to rapid capture of the PKA catalytic subunit limiting signaling duration. Overall, the biochemical data and modeling support the conclusions although a few details can be addressed further and the in vivo data remains preliminary. The work nevertheless presents exciting findings that provide a tantalizing mechanism to selectively modulate PKA activity at precise subcellular locations.

  (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

Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

1. Florian Kabinger
2. Carina Stiller
3. Jana Schmitzová
4. Christian Dienemann
5. Goran Kokic
6. Hauke S. Hillen
7. Claudia Höbartner
8. Patrick Cramer

Reviewed by ScreenIT

Nanopore Dwell Time Analysis Permits Sequencing and Conformational Assignment of Pseudouridine in SARS-CoV-2

1. Aaron M. Fleming
2. Nicole J. Mathewson
3. Shereen A. Howpay Manage
4. Cynthia J. Burrows

Reviewed by ScreenIT

The method utilized to purify the SARS-CoV-2 N protein can affect its molecular properties

1. Aneta Tarczewska
2. Marta Kolonko-Adamska
3. Mirosław Zarębski
4. Jurek Dobrucki
5. Andrzej Ożyhar
6. Beata Greb-Markiewicz

Reviewed by ScreenIT

In-solution buffer-free digestion for the analysis of SARS-CoV-2 RBD proteins allows a full sequence coverage and detection of post-translational modifications in a single ESI-MS spectrum

1. Luis Ariel Espinosa
2. Yassel Ramos
3. Ivan Andújar
4. Enso Onill Torres
5. Gleysin Cabrera
6. Alejandro Martín
7. Diamilé González
8. Glay Chinea
9. Mónica Becquet
10. Isabel González
11. Camila Canaán-Haden
12. Elías Nelson
13. Gertrudis Rojas
14. Beatriz Pérez-Massón
15. Dayana Pérez-Martínez
16. Tamy Boggiano
17. Julio Palacio
18. Sum Lai Lozada-Chang
19. Lourdes Hernández
20. Kathya Rashida de la Luz Hernández
21. Saloheimo Markku
22. Vitikainen Marika
23. Yury Valdés-Balbín
24. Darielys Santana-Medero
25. Daniel G. Rivera
26. Vicente Vérez-Bencomo
27. Mark Emalfarb
28. Ronen Tchelet
29. Gerardo Guillén
30. Miladys Limonta
31. Eulogio Pimentel
32. Marta Ayala
33. Vladimir Besada
34. Luis Javier González

Reviewed by ScreenIT

Permeant fluorescent probes visualize the activation of SARM1 and uncover an anti-neurodegenerative drug candidate

1. Wan Hua Li
2. Ke Huang
3. Yang Cai
4. Qian Wen Wang
5. Wen Jie Zhu
6. Yun Nan Hou
7. Sujing Wang
8. Sheng Cao
9. Zhi Ying Zhao
10. Xu Jie Xie
11. Yang Du
12. Chi-Sing Lee
13. Hon Cheung Lee
14. Hongmin Zhang
15. Yong Juan Zhao

• Curated by eLife

  Evaluation Summary:

  SARM1, an enzyme that can convert NAD+ to ADP-ribose or cyclic ADP-ribose, is implicated in axon degeneration. This manuscript describes the development of small molecule probes that can detect the activity of SARM1 in live cells. In the course of the work, a small molecule derived from an hypertension drug was discovered as an effective SARM1 inhibitor. Although the activity probes are novel, the mechanism of SARM1 inactivation by dHNN has not been established. The probe and the inhibitor described in the manuscript could lead to future therapeutic development targeting SARM1 to treat axon degeneration.

  (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

Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite

1. Gabriele Cerutti
2. Yicheng Guo
3. Tongqing Zhou
4. Jason Gorman
5. Myungjin Lee
6. Micah Rapp
7. Eswar R. Reddem
8. Jian Yu
9. Fabiana Bahna
10. Jude Bimela
11. Yaoxing Huang
12. Phinikoula S. Katsamba
13. Lihong Liu
14. Manoj S. Nair
15. Reda Rawi
16. Adam S. Olia
17. Pengfei Wang
18. Baoshan Zhang
19. Gwo-Yu Chuang
20. David D. Ho
21. Zizhang Sheng
22. Peter D. Kwong
23. Lawrence Shapiro

Reviewed by ScreenIT