Biophysics

Tracing the substrate translocation mechanism in P-glycoprotein

1. Theresa Gewering
2. Deepali Waghray
3. Kristian Parey
4. Hendrik Jung
5. Nghi NB Tran
6. Joel Zapata
7. Pengyi Zhao
8. Hao Chen
9. Dovile Januliene
10. Gerhard Hummer
11. Ina Urbatsch
12. Arne Moeller
13. Qinghai Zhang

• Curated by eLife

  eLife assessment

  P-glycoprotein is a major ABC-transporter that exports drugs used in chemotherpay and effects the pharmacokinetics of other drugs. Here the authors have determined cryo-EM structures of drug complexes in previously unforeseen outward-facing conformations. These convincing findings are mechanistically important and reveal potential regions to be exploited by rational-based drug design.

Reviewed by eLife

CryoEM structures of the human CLC-2 voltage-gated chloride channel reveal a ball-and-chain gating mechanism

1. Mengyuan Xu
2. Torben Neelands
3. Alexander S Powers
4. Yan Liu
5. Steven D Miller
6. Grigore D Pintilie
7. J Du Bois
8. Ron O Dror
9. Wah Chiu
10. Merritt Maduke

• Curated by eLife

  eLife assessment

  This study examines the human voltage-gated chloride channel CLC-2. A combination of cryo-EM, electrophysiology, and computational analysis provides compelling support for a "ball and chain" mechanism of inactivation. This and other findings regarding the gating and inhibition mechanisms of the channel are of fundamental interest to ion channel physiologists.

Reviewed by eLife

Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM

1. Cathrine Bergh
2. Urška Rovšnik
3. Rebecca Howard
4. Erik Lindahl

• Curated by eLife

  eLife assessment

  The authors use a combination of structural and MD simulation approaches to characterize phospholipid interactions with the pentameric ligand-gated ion channel, GLIC. The general agreement between structures and simulations increases confidence in the description of the lipid interaction poses and provides a solid basis for the prediction of a state-dependent interaction site where lipids could dynamically modulate channel gating. The results will be very useful to understand the nature of phospholipid interactions with pentameric ligand-gated ion channels, although the functional or structural significance of these lipid interactions remains to be verified.

Reviewed by eLife

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