Biophysics

Thermal analysis of protein stability and ligand binding in complex media

1. Matthew W. Eskew
2. Albert S. Benight

Reviewed by ScreenIT

SARS-CoV-2 variants impact RBD conformational dynamics and ACE2 accessibility

1. Mariana Valério
2. Luís Borges-Araújo
3. Manuel N. Melo
4. Diana Lousa
5. Cláudio M. Soares

Reviewed by ScreenIT

In silico study on the effects of disulfide bonds in ORF8 of SARS-CoV-2

1. Yadi Cheng
2. Xubiao Peng

Reviewed by ScreenIT

Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond

1. Márton A Simon
2. László Csanády

• Curated by eLife

  Evaluation Summary:

  Multiple inherited mutations in the epithelial CFTR anion-permeable channel cause cystic fibrosis through different molecular mechanisms that can be targeted by different types of drugs to treat the disease. Drawing from available structural information and double-mutant cycle analysis of patch-clamp recordings, Simon and Csanády find that one of the most common CFTR disease-causing mutations, R117H, disrupts an interaction between the R117 side-chain and a main-chain carbonyl that selectively stabilizes the open state of the channel. These findings may open new paths of exploration for treating patients carrying this mutation, and provide important mechanistic constraints towards understanding the gating mechanism of CFTR proteins.

  (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

Probing the mutational landscape of the SARS-CoV-2 spike protein via quantum mechanical modeling of crystallographic structures

1. Marco Zaccaria
2. Luigi Genovese
3. William Dawson
4. Viviana Cristiglio
5. Takahito Nakajima
6. Welkin Johnson
7. Michael Farzan
8. Babak Momeni

Reviewed by ScreenIT

Label-free imaging of M1 and M2 macrophage phenotypes in the human dermis in vivo using two-photon excited FLIM

1. Marius Kröger
2. Jörg Scheffel
3. Evgeny A Shirshin
4. Johannes Schleusener
5. Martina C Meinke
6. Jürgen Lademann
7. Marcus Maurer
8. Maxim E Darvin

• Curated by eLife

  Evaluation Summary:

  Kröger et al use 2-photon FLIM tomography to perform correlative imaging on in vitro, ex vivo and in vivo blood and skin cells to determine characteristic NADPH fluorescence lifetimes for M1 and M2 ends of macrophage spectrum. Interestingly, M1 and M2 macrophages, and all other tissue cells, had distinctive lifetime features leading to robust prediction of phenotypes, with ground trust defined by cytokine staining. They generate a decision tree that has ~90% accuracy in identifying M1 and M2 based on FLIM parameters and additional information. The ability to use two photon fluorescence lifetime tomography of NADPH fluorescence to identify macrophages and their inflammatory status in human tissues should open opportunities in experimental medicine and eventually medical diagnosis.

  (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

The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism

1. Elena B. Riel
2. Björn C. Jürs
3. Sönke Cordeiro
4. Marianne Musinszki
5. Marcus Schewe
6. Thomas Baukrowitz

Reviewed by Biophysics Colab

Allosteric modulation of the adenosine A2A receptor by cholesterol

1. Shuya Kate Huang
2. Omar Almurad
3. Reizel J Pejana
4. Zachary A Morrison
5. Aditya Pandey
6. Louis-Philippe Picard
7. Mark Nitz
8. Adnan Sljoka
9. R Scott Prosser

• Curated by eLife

  Evaluation Summary:

  Cholesterol has long been known to have significant effects on G protein-coupled receptor (GPCR) ligand binding properties and stability, and cholesterol/GPCR interactions have frequently been observed in high-resolution structures. However, relatively limited biophysical work has been done to investigate the mechanistic basis for cholesterol's effects. This manuscript describes the use of a sensitive 19F NMR probe to monitor conformational equilibria in a prototypical GPCR, the A2a adenosine receptor. These experiments, together with data from other NMR experiments, computational analysis, and G protein assays, show that the subtle effects of cholesterol derive in large part from modulation of membrane biophysical properties, in contrast to conventional allosteric modulators that exert their effects through direct long-lived receptor binding.

  (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

pH-dependent 11° F1FO ATP synthase sub-steps reveal insight into the FO torque generating mechanism

1. Seiga Yanagisawa
2. Wayne D Frasch

• Curated by eLife

  Evaluation Summary:

  This paper is of outstanding interest to the broad community of scientists interested in biological energy conversion in general and rotary ATPases in particular. The authors show that the 36{degree sign} power stroke in ATP synthesis is subdivided into two steps of 11{degree sign} and 25{degree sign} in the E. coli enzyme, which serves as a comparatively simple model of the fundamental and universally important process of ATP production in mitochondria and chloroplasts. By combining precise and sophisticated single-molecule studies with directed mutagenesis, this work provides the much-needed functional context for recent high-resolution cryo-EM structures of rotary 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 #2 agreed to share their name with the authors.)

Reviewed by eLife

#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol

1. Abigail Dommer
2. Lorenzo Casalino
3. Fiona Kearns
4. Mia Rosenfeld
5. Nicholas Wauer
6. Surl-Hee Ahn
7. John Russo
8. Sofia Oliveira
9. Clare Morris
10. Anthony Bogetti
11. Anda Trifan
12. Alexander Brace
13. Terra Sztain
14. Austin Clyde
15. Heng Ma
16. Chakra Chennubhotla
17. Hyungro Lee
18. Matteo Turilli
19. Syma Khalid
20. Teresa Tamayo-Mendoza
21. Matthew Welborn
22. Anders Christensen
23. Daniel GA Smith
24. Zhuoran Qiao
25. Sai K Sirumalla
26. Michael O’Connor
27. Frederick Manby
28. Anima Anandkumar
29. David Hardy
30. James Phillips
31. Abraham Stern
32. Josh Romero
33. David Clark
34. Mitchell Dorrell
35. Tom Maiden
36. Lei Huang
37. John McCalpin
38. Christopher Woods
39. Alan Gray
40. Matt Williams
41. Bryan Barker
42. Harinda Rajapaksha
43. Richard Pitts
44. Tom Gibbs
45. John Stone
46. Daniel M. Zuckerman
47. Adrian J. Mulholland
48. Thomas Miller
49. Shantenu Jha
50. Arvind Ramanathan
51. Lillian Chong
52. Rommie E Amaro

Reviewed by ScreenIT