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 ...

The development of a universal protein coarse-grained model has been a long-standing challenge. A coarse-grained model with chemical transferability has now been developed by combining deep-learning m...

Hsp70s use energy from ATP hydrolysis to unfold protein structures and solubilize stable aggregates and accumulate native species, even under adverse non-native conditions. To carry out its catalytic ...

Chaperones ensure protein homeostasis and are conserved across species. The ATP-dependent chaperone Hsp90 is present from bacteria to eukaryotes, where it stabilizes and activates a wide range of subs...

The phosphorylation of the microtubule-associated tau protein plays a key role in the regulation of its physiological function. In particular, tau hyperphosphorylation affects its binding to the tubulin surface, destabilizing the tau-microtubule interface and leading to the accumulation of fibrillar aggregates in the brain. In this work, we performed classical molecular dynamics simulations for the tau-R2/tubulin assembly with various phosphorylation states of serines 285, 289, and 293. We analyze the resulting trajectories to obtain a detailed view of the protein interface in the complex and the impact of tau phosphorylations on the stability of this assembly and on the mobility of the tubulin disordered C-terminal tails (CTTs). We show how the tubulin CTTs help maintain the tau-R2 fragment on the tubulin surface despite the destabilizing effect induced by phosphorylations. Conversely, tau phosphorylation affects the CTTs’ flexibility and their potential activity as MAP-recruiting hooks. Furthermore, counterion-mediated bridges between the phosphate groups and tubulin glutamates also contribute to the binding of tau-R2 on the MT. Overall, the complex dynamics of this fuzzy phosphorylated assembly shed new light on the importance of the cytoplasmic environment in neurons in the context of Alzheimer’s disease.