Biophysics

C9orf72 polyPR directly binds to various nuclear transport components

1. Hamidreza Jafarinia
2. Erik van der Giessen
3. Patrick R Onck

• Curated by eLife

  eLife assessment

  This study provides an important starting point for unraveling the molecular basis of the pathological phenotypes of the repeat expansion in the gene associated with open reading frame 72 in human chromosome 9. The coarse-grained simulation method used by the authors goes beyond the state of the art, investigating a compelling number of binding partners. The evidence supporting the claims of the authors is solid, although experimental validation of the results would strengthen the major conclusions of the work. The work will be of broad interest to biophysicists and biochemists.

Reviewed by eLife

Diameter dependence of transport through nuclear pore complex mimics studied using optical nanopores

1. Nils Klughammer
2. Anders Barth
3. Maurice Dekker
4. Alessio Fragasso
5. Patrick R Onck
6. Cees Dekker

• Curated by eLife

  eLife assessment

  This important study reports on a new method for the fabrication and the analysis of the transport through nuclear pore complexes mimic. Methods, data and analyses are convincing and show a clear correlation between the size of the nuclear pore complex mimic and its transport selectivity. This work will be of high interest to biologists and biophysicists working on the mechanosensitivity of nucleocytoplasmic transport.

Reviewed by eLife

Structural and mechanistic insights into ribosomal ITS2 RNA processing by nuclease-kinase machinery

1. Jiyun Chen
2. Hong Chen
3. Shanshan Li
4. Xiaofeng Lin
5. Rong Hu
6. Kaiming Zhang
7. Liang Liu

• Curated by eLife

  eLife assessment

  This study represents a valuable mechanistic contribution towards understanding how ribosomal RNA is processed during ribosome biogenesis. The biochemical evidence supporting the major conclusions is convincing. This work will be of interest to cell biologists and biochemists working on ribosome biogenesis.

Reviewed by eLife

Biased activation of the vasopressin V2 receptor probed by NMR, paramagnetic ligands, and molecular dynamics simulations

1. Gérald Gaibelet
2. Aurélien Fouillen
3. Stéphanie Riché
4. Hélène Orcel
5. Christiane Mendre
6. Ali Kanso
7. Romain Lanotte
8. Julie Nguyen
9. Juliette Dimon
10. Serge Urbach
11. Rémy Sounier
12. Sébastien Granier
13. Dominique Bonnet
14. Xiaojing Cong
15. Bernard Mouillac
16. Hélène Déméné

Reviewed by PREreview

Free volume theory explains the unusual behavior of viscosity in a non-confluent tissue during morphogenesis

1. Rajsekhar Das
2. Sumit Sinha
3. Xin Li
4. TR Kirkpatrick
5. D Thirumalai

• Curated by eLife

  eLife assessment

  This fundamental study substantially advances our physical understanding of the sharp increase and saturation of the viscosity of non-confluent tissues with increasing cell density. Through the analysis of a simplified model this study provides compelling evidence that polydispersity in cell size and the softness of cells together can lead to this phenomenon. The work will be of general interest to biologists and biophysicists working on development.

Reviewed by eLife

Exploring the K+ binding site and its coupling to transport in the neurotransmitter:sodium symporter LeuT

1. Solveig G Schmidt
2. Andreas Nygaard
3. Joseph A Mindell
4. Claus J Loland

• Curated by eLife

  eLife assessment

  The bacterial neurotransmitter:sodium symporter homoglogue LeuT is an well-established model system for understanding the fundamental basis for how human monoamine transporters, such as the dopamine and serotonin, couple ions with neurotransmitter uptake. Here the authors provide convincing data to show that K+ binding on the intraceullular side catalyses the return step of the transport cycle in LeuT by binding to one of the two sodium sites. The mechansitic consequences of K+ binding could either facilitate LeuT re-setting and/or prevent the rebinding and possible efflux of Na+ and substrate.

Reviewed by eLife

Energetics of the microsporidian polar tube invasion machinery

1. Ray Chang
2. Ari Davydov
3. Pattana Jaroenlak
4. Breane Budaitis
5. Damian C Ekiert
6. Gira Bhabha
7. Manu Prakash

• Curated by eLife

  eLife assessment

  This important study combines experiments and fluid mechanics modeling to determine the mechanism of the ultrafast ejection of the polar tube of the Microsporidia parasite and of transport through this tube. The methods and the analysis, based on the variation of the viscosity of the external medium, are compelling and allow for the first time to discriminate among proposed ejection mechanisms. This approach where simple physical principles are used for distinguishing between mechanisms when the precise geometry is inaccessible through imaging is potentially applicable to other systems in microbiology.

Reviewed by eLife

Multiscale effects of perturbed translation dynamics inform antimalarial design

1. Leonie Anton
2. Wenjing Cheng
3. Meseret T. Haile
4. David W. Cobb
5. Xiyan Zhu
6. Leyan Han
7. Emerson Li
8. Anjali Nair
9. Carolyn L. Lee
10. Hangjun Ke
11. Guoan Zhang
12. Emma H. Doud
13. Chi-Min Ho

Reviewed by Rapid Reviews Infectious Diseases

Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure

1. KM Rifat Faysal
2. James C Walsh
3. Nadine Renner
4. Chantal L Márquez
5. Vaibhav B Shah
6. Andrew J Tuckwell
7. Michelle P Christie
8. Michael W Parker
9. Stuart G Turville
10. Greg J Towers
11. Leo C James
12. David A Jacques
13. Till Böcking

• Curated by eLife

  eLife assessment

  In this important study, the authors propose that lenacapavir inhibits HIV-1 replication by inducing "lethal hyperstabilization" of the capsid, based on experiments that clearly demonstrate such an effect at high drug concentrations. Data supporting the model are incomplete at low drug concentrations, and a firm correlation between the in vitro effects and therapeutic mechanism of action has not yet been established.

Reviewed by eLife

Asymmetric framework motion of TCRαβ controls load-dependent peptide discrimination

1. Ana C Chang-Gonzalez
2. Robert J Mallis
3. Matthew J Lang
4. Ellis L Reinherz
5. Wonmuk Hwang

• Curated by eLife

  eLife assessment

  Using extensive atomistic molecular dynamics simulations, the authors analyzed the TCR/pMHC interface with different peptide sequences and protein constructs. The results provide important insights into the catch-bond phenomenon in the context of T-cell activation. In particular, the analysis points to convincing evidence that supports the role of force in further discriminating different peptides during the activation process beyond structural considerations.

Reviewed by eLife