Biophysics

TRPML1 gating modulation by allosteric mutations and lipids

1. Ninghai Gan
2. Yan Han
3. Weizhong Zeng
4. Youxing Jiang

• Curated by eLife

  eLife Assessment

  Transient receptor potential mucolipin 1 (TRPML1) functions as a lysosomal ion channel whose variants are associated with lysosomal storage disorder mucolipidosis type IV. This important report describes local and global structural changes driven by binding of regulatory phospholipids and by mutations that allosterically cause gain or loss of channel function. Most of the claims related to the allosteric regulation of TRPML1 are convincingly supported by two new cryo-EM structures which are evaluated within the context of previously reported TRPML1 structures, and a proposed allosteric gating mechanism is partially supported by functional electrophysiology results.

Reviewed by eLife

Water and chloride as allosteric inhibitors in WNK kinase osmosensing

1. Liliana R Teixeira
2. Radha Akella
3. John M Humphreys
4. Haixia He
5. Elizabeth J Goldsmith

• Curated by eLife

  eLife Assessment

  This study presents an important investigation of water coordination in a specific kinase family with a focus on the regulation of osmosensing protein kinases. X-ray crystallographic approaches combined with functional assays are used to address the hypothesis that bound water participates in the osmosensing mechanism as an allosteric kinase inhibitor. The evidence for changes in kinase conformation and space group of the crystal as a function of added low molecular weight polyethylene glycol is solid. The work will be of considerable interest to the kinase field as well as colleagues studying allosteric regulation of protein function.

Reviewed by eLife

Feeding Rates in Sessile versus Motile Ciliates are Hydrodynamically Equivalent

1. Jingyi Liu
2. Yi Man
3. John H Costello
4. Eva Kanso

• Curated by eLife

  eLife Assessment

  This important paper addresses the role of fluid flows in nutrient uptake by microorganisms propelled by the action of cilia or flagella. Using a range of mathematical models for the flows created by such appendages, the authors provide convincing evidence that the two strategies of swimming and sessile motion can be competitive. These results will have significant implications for our understanding of the evolution of multicellularity in its various forms.

Reviewed by eLife

Electrostatic interactions in nucleosome and higher-order structures are regulated by protonation state of histone ionizable residue

1. Houfang Zhang
2. Wenhan Guo
3. Wang Xu
4. Anbang Li
5. Lijun Jiang
6. Lin Li
7. Yunhui Peng

• Curated by eLife

  eLife assessment

  This important study explores the impact of pH changes and cancer mutations on nucleosome interactions and higher-order chromatin structures. The evidence supporting the main conclusions is solid, based on rigorous computational methods, including pKa prediction, electrostatic force calculation, and molecular dynamics simulations. The findings provide insights into how protonation states and cancer-associated mutations affect nucleosome electrostatics and chromatin organization, making this work of broad interest to chromatin biologists, cancer researchers, and computational biophysicists.

Reviewed by eLife

Probing the modulation of enzyme kinetics by multi-temperature, time-resolved serial crystallography

1. Eike C. Schulz
2. Andreas Prester
3. David von Stetten
4. Gargi Gore
5. Caitlin E. Hatton
6. Kim Bartels
7. Jan-Philipp Leimkohl
8. Hendrik Schikora
9. Helen M. Ginn
10. Friedjof Tellkamp
11. Pedram Mehrabi

Reviewed by PREreview

Massively parallel genetic perturbation reveals the energetic architecture of an amyloid beta nucleation reaction

1. Anna Arutyunyan
2. Mireia Seuma
3. Andre J. Faure
4. Benedetta Bolognesi
5. Ben Lehner

Reviewed by PREreview

Connecting Chromatin Structures to Gene Regulation Using Dynamic Polymer Simulations

1. Yi Fu
2. Tianxiao Zhao
3. Finnegan Clark
4. Sofia Nomikou
5. Aristotelis Tsirigos
6. Timothée Lionnet

• Curated by eLife

  eLife assessment

  This study presents a valuable optimization algorithm to identify polymer models that best fit population-averaged chromosome contact data that will be of interest to physicists and biologists working on chromatin organization. The conclusions are supported by solid evidence.

Reviewed by eLife

Molecular Insights into Single-Chain Lipid Modulation of Acid-Sensing Ion Channel 3

1. Ramya Bandarupalli
2. Rebecca Roth
3. Robert C Klipp
4. John R Bankston
5. Jing Li

Reviewed by Arcadia Science

Predicting the sequence-dependent backbone dynamics of intrinsically disordered proteins

1. Sanbo Qin
2. Huan-Xiang Zhou

• Curated by eLife

  eLife assessment

  In this useful study, a solid machine learning approach based on a broad set of systems to predict the R2 relaxation rates of residues in intrinsically disordered proteins (IDPs) is described. The ability to predict the patterns of R2 will be helpful to guide experimental studies of IDPs. A potential weakness is that the predicted R2 values may include both fast and slow motions, thus the predictions provide only limited new physical insights into the nature of the underlying protein dynamics, such as the most relevant timescale.

Reviewed by eLife

PUFA stabilizes a conductive state of the selectivity filter in IKs channels

1. Alessia Golluscio
2. Jodene Eldstrom
3. Jessica J Jowais
4. Marta Elena Perez
5. Kevin Peter Cunningham
6. Alicia De La Cruz
7. Xiaoan Wu
8. Valentina Corradi
9. D Peter Tieleman
10. David Fedida
11. H Peter Larsson

• Curated by eLife

  eLife assessment

  This manuscript reveals an important mechanism of KCNQ1/IKs channel gating and PUFA modulation of this mechanism. This mechanism is supported by convincing single channel recordings, macroscopic current recordings and mutational analyses. These findings are of importance to the ion channel field and possibly future therapeutic applications.

Reviewed by eLife