Biophysics

Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove

1. Christina Alexandra Stephens
2. Niek van Hilten
3. Lisa Zheng
4. Michael Grabe

• Curated by eLife

  eLife Assessment

  This important study provides information on the TMEM16 family of membrane proteins, which play roles in lipid scrambling and ion transport. By simulating 27 structures representing five distinct family members, the authors captured hundreds of lipid scrambling events, offering insights into the mechanisms of lipid translocation and the specific protein regions involved in these processes. However, while the data on groove dilation is compelling, the evidence for outside-the-groove scramblase activity without experimental validation is inadequate and is based on a limited set of observed events.

Reviewed by eLife

Flexibility in PAM recognition expands DNA targeting in xCas9

1. Kazi A Hossain
2. Lukasz Nierzwicki
3. Modesto Orozco
4. Jacek Czub
5. Giulia Palermo

• Curated by eLife

  eLife Assessment

  This manuscript describes a fundamental investigation of the functioning of Cas9 and in particular on how variant xCas9 expands DNA targeting ability by an increase-flexibility mechanism. The authors provide compelling evidence to support their mechanistic models and the relevance of flexibility and entropy in recognition. This work can be of interest to a broad community of structural biophysicists, computational biologists, chemists, and biochemists.

Reviewed by eLife

Expanding Automated Multiconformer Ligand Modeling to Macrocycles and Fragments

1. Jessica Flowers
2. Nathaniel Echols
3. Galen Correy
4. Priya Jaishankar
5. Takaya Togo
6. Adam R Renslo
7. Henry van den Bedem
8. James S Fraser
9. Stephanie A Wankowicz

• Curated by eLife

  eLife Assessment

  This work presents a valuable extension of qFit-ligand, a computational method for modeling conformational heterogeneity of ligands in X-ray crystallography and cryo-EM density maps. The evidence presented for improved capabilities through careful validation against the previous version, notably in expanding ligand sampling within the conformational space, is solid yet still incomplete. The enhanced methodology demonstrates practical utility for challenging applications, including macrocyclic compound modeling and crystallographic drug fragment screening.

Reviewed by eLife

Mechanical stresses govern myoblast fusion and myotube growth

1. Yoann Le Toquin
2. Sushil Dubey
3. Aleksandra Ardaševa
4. Lakshmi Balasubramaniam
5. Emilie Delaune
6. Valérie Morin
7. Amin Doostmohammadi
8. Christophe Marcelle
9. Benoît Ladoux

Reviewed by preLights

Cell cycle and Age-Related Modulations of Mouse Chromosome Stiffness

1. Ning Liu
2. Wenan Qiang
3. Philip Jordan
4. John F. Marko
5. Huanyu Qiao

• Curated by eLife

  eLife Assessment

  This valuable paper describes the stiffness of meiotic chromosomes in both oocytes and spermatocytes. The authors identify differences in stiffness between meiosis I and II chromosomes, as well as an age-dependent increase in stiffness in meiosis I (and meiosis II) chromosomes, results that are highly significant for the field of chromosome biology. The report is, however, mostly descriptive and the mechanisms underlying age-dependent changes in chromosome stiffness remain unclear. The evidence suggesting that changes in stiffness are independent of cohesin, which is known to deteriorate with age, is still incomplete.

Reviewed by eLife