Bacterial pathogens must withstand metal-induced stress during infection, yet the mechanisms by which they sense and respond to toxic metal ions remain incompletely understood. Here, we uncover a prev...

FeNNol Pretrained Models Collection. Contribute to FeNNol-tools/FeNNol-PMC development by creating an account on GitHub.

Phosphorylation is a major post-translational modification that is involved in the regulation of the dynamics and function of intrinsically disordered proteins (IDPs). We recently characterized a phen...

Multi-scale molecular dynamics simulations reveal that polymyxins form polymyxin-protein aggregates upon associating with the E. coli outer membrane thereby reducing lateral mobility of outer membrane...

The biological importance of intrinsically disordered proteins (IDPs) has been established for over two decades, yet these systems remain difficult to characterize, as they are better described by conformational ensembles instead of a single reference structure for their folded counterparts. Tau is a prominent member of the IDP family, which sees its cellular function regulated by multiple phosphorylation sites and whose hyperphosphorylation is involved in neurodegenerative diseases such as Alzheimer’s. We used coarse-grain MD simulations with the CALVADOS model to investigate the conformational landscape of tau without and with phosphorylations. Characterizing the local compactness of IDPs allows us to highlight how disorder comes in various flavors, as we can define different domains along the tau sequence. We define the IDP’s Statistical Tertiary Organization (STO) as the average spatial arrangements of domains, which constitute an extension of the tertiary structure of folded proteins. We also use IDP-specific metrics to characterize the local curvature and flexibility of tau. Comparing the local flexibilities with T2 relaxation times from NMR experiments, we show how this metric is related to the protein dynamics. A curvature and flexibility pattern in the repeat domains can also be connected to tau binding properties, without having to explicitly model the protein’s interaction partner. Finally, we rediscuss the original paperclip model that describes the spatial organization of tau and how phosphorylations impact it. The resulting changes in the protein intradomain and interdomain interaction pattern allow us to propose experimental setups to test our hypothesis.

Faut-il forcément des microscopes et des tubes à essai pour observer des molécules ou des protéines ?

Tuberculosis remains the deadliest infectious disease caused by a single pathogen, highlighting the urgent need for novel therapies. A deeper under...

Nature Structural & Molecular Biology - Liu et al. show that SPIN90 dimerizes and binds two Arp2/3 complexes to nucleate two bidirectional actin filaments and the dimerization domain is...

Glycolipids from pathogenic Mycobacterium tuberculosis play important roles during the interaction of the pathogen with macrophages and can shape the …

ADAM10 is a crucial membrane-bound metalloprotease that regulates cellular physiology by cleaving and releasing membrane-anchored proteins, including adhesion molecules and growth factor precursors, t...

Deep eutectic solvents (DESs) are often promoted as a more environmentally friendly alternative for ionic liquids and other ionic solvents. Like ionic liquids, DESs can be designed for specific tasks ...