Biophysics

Molecular determinants of complexin clamping and activation function

1. Manindra Bera
2. Sathish Ramakrishnan
3. Jeff Coleman
4. Shyam S Krishnakumar
5. James E Rothman

• Curated by eLife

  Evaluation Summary:

  Berra and colleagues revisit several mechanistic questions mainly centered on the accessory helix of mouse complexin (mCpx) and its contribution to the 'fusion clamp' property of mCpx whereby mCpx-SNARE interactions prevent full assembly and subsequent membrane fusion. This clamping function is believed to help generate a metastable pool of release-ready vesicles at the synapse, and it has been studied in a wide variety of systems including mouse, fly, worm, squid, fish, and diverse in vitro biochemical preps over the past ~ 20 years. The authors derive several conclusions from their efforts, but most relevant is a reiteration of a previous proposal that the accessory helix region of mCpx stabilizes a pre-fusion clamped state via interactions with SNAREs.

  (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

A strategy to optimize the peptide-based inhibitors against different mutants of the spike protein of SARS-CoV-2

1. Prerna Priya
2. Abdul Basit
3. Pradipta Bandyopadhyay

Reviewed by ScreenIT

Omicron and Alpha P680H block SARS-CoV2 spike protein from accessing cholinergic inflammatory pathway via α9-nAChR mitigating the risk of MIS-C

1. Ulises Santiago
2. Carlos J. Camacho

Reviewed by ScreenIT

Biophysical Fitness Landscape of the SARS-CoV-2 Delta Variant Receptor Binding Domain

1. Casey Patrick
2. Vaibhav Upadhyay
3. Alexandra Lucas
4. Krishna M.G. Mallela

Reviewed by ScreenIT

Effect of an amyloidogenic SARS-COV-2 protein fragment on α-synuclein monomers and fibrils

1. Asis K. Jana
2. Chance W. Lander
3. Andrew D. Chesney
4. Ulrich H. E. Hansmann

Reviewed by ScreenIT

How to assemble a scale-invariant gradient

1. Arnab Datta
2. Sagnik Ghosh
3. Jane Kondev

• Curated by eLife

  Evaluation Summary:

  How biological patterns such as concentration gradient scale with the size of the cell or organism is a long-standing question in developmental and cell biology. In this study, Datta et al show theoretically that directed membrane transport of biomolecules and their release at the cell pole results in a cytoplasmic gradient that scales with cell size if two requirements are met: the cell grows while maintaining its spheroid proportions, (i.e. not by elongation), and the binding of the cytoplasmic fraction of the biomolecule to the membrane should be close to irreversible. A strength of this manuscript is that it invokes a realistic cellular mechanism that could be achieved through several biochemical implementations and can inspire experimental studies. Stronger biological examples and a deeper search in the literature or change in some of the simulation parameters would improve the study, and give the "impetus for experiments" the authors wish to provide.

  (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

A Possible Way to Relate the Effects of SARS-CoV-2-Induced Changes in Transferrin to Severe COVID-19-Associated Diseases

1. Elek Telek
2. Zoltán Ujfalusi
3. Gábor Kemenesi
4. Brigitta Zana
5. Ferenc Jakab
6. Gabriella Hild
7. András Lukács
8. Gábor Hild

Reviewed by ScreenIT

Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility

1. Anacleto Silva de Souza
2. Vitor Martins de Freitas Amorim
3. Robson Francisco de Souza
4. Cristiane Rodrigues Guzzo

Reviewed by ScreenIT

Contingency and selection in mitochondrial genome dynamics

1. Christopher J Nunn
2. Sidhartha Goyal

• Curated by eLife

  Evaluation Summary:

  This study uses long-read sequencing to investigate the origin of spontaneous petite mutants in S. cerevisiae. The results illustrate how the S. cerevisiae mitochondrial genome is prone to recombination events that lead to the formation of complex concatemers of fragments of the mitochondrial DNA that contain a high density of replication origins and, as a result, may outcompete the full mitochondrial genome. Apart from confirming existing hypotheses about the nature of petite mutants and revealing the structural diversity of rho-mitochondrial DNA, the results also allow drawing parallels to the origins of mitochondrial mutations in other organisms.

  (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

Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels

1. Michaela A Edmond
2. Andy Hinojo-Perez
3. Xiaoan Wu
4. Marta E Perez Rodriguez
5. Rene Barro-Soria

• Curated by eLife

  Evaluation Summary:

  This study investigates the mechanism of voltage-dependent activation of the KCNQ class of potassium channels that regulate neuronal firing, and are mutated in monogenic forms of epilepsy. This study makes an important technical step forward by reporting measurements of voltage-dependent conformational changes of KCNQ2/Kv7.2 channels, measurements which are known to be extremely difficult for this biologically important channel. Understanding these conformational changes allows the authors to investigate models of how voltage-dependent changes are coupled to opening of the channel pore, and also identify diverse mechanisms by which disease-linked mutations of KCNQ2/Kv7.2 may alter channel 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 #1 agreed to share their name with the authors.)

Reviewed by eLife