BJ Articles Ahead of Print

Mechanical signals regulate functions of mechanosensitive proteins by inducing structural changes that are determinant for force-dependent interactions. Talin is a focal adhesion protein which is known to extend under mechanical load and it has been shown to unfold via intermediate states. Here, we compared different non-equilibrium Molecular Dynamics (MD) simulations to study unfolding of the talin rod. We combined boxed MD (BXD), Steered MD (SMD) and Umbrella Sampling (US) techniques and provide free energy profiles for unfolding of talin rod subdomains.

Protein/lipid co-assembly is an understudied phenomenon that is important to the function of antimicrobial peptides as well as the pathological effects of amyloid. Here we study the co-assembly process of PAP248-286, a seminal peptide that displays both amyloid-forming and antimicrobial activity. PAP248-286 is a peptide fragment of prostatic acid phosphatase and has been reported to form amyloid fibrils, known as semen-derived enhancer of viral infection (SEVI), that enhance the viral infectivity of HIV.

The sarcoplasmic reticulum Ca2+-ATPase (SERCA) transports two Ca2+ ions from the cytoplasm to the reticulum lumen at the expense of ATP hydrolysis. In addition to transporting Ca2+, SERCA facilitates bidirectional proton transport across the sarcoplasmic reticulum to maintain the charge balance of the transport sites and to balance the charge deficit generated by the exchange of Ca2+. Previous studies have shown the existence of a transient water-filled pore in SERCA that connects the Ca2+-binding sites with the lumen, but the capacity of this pathway to sustain passive proton transport has remained unknown.

Cell membranes mainly consist of lipid bilayers with an actively regulated composition. The underlying processes are still poorly understood, in particular how the hundreds of components are controlled. Cholesterol has been found to correlate with phospholipid saturation, for reasons that remain unclear. To better understand the link between cell-membrane regulation and chemical composition, we establish a computational framework based on chemical reaction networks, resulting in multiple semi-grand canonical ensembles.

Cytoplasmic dynein is a eukaryotic motor protein complex that, along with its regulatory protein dynactin, is essential to the transport of organelles within cells. The interaction of dynein with dynactin is regulated by binding between the intermediate chain (IC) subunit of dynein and the p150Glued subunit of dynactin. Even though in the rat versions of these proteins this interaction primarily involves the single α-helix (SAH) region at the N-terminus of IC, in Drosophila and yeast ICs the removal of a nascent helix (H2) downstream of the SAH considerably diminishes IC/p150Glued complex stability.

Integrins are heterodimeric transmembrane proteins that mediate cellular adhesion and bidirectional mechanotransductions through their conformational allostery. The allosteric pathway of an I domain-containing integrin remains unclear because of its complexity and lack of effective experiments. For a typical I domain-containing integrin αXβ2, molecular dynamics simulations were employed here to investigate the conformational dynamics in the first two steps of outside-in activation, the bindings of both the external and internal ligands.

(Biophysical Journal 115, 2301–2309; December 18, 2018)

Transcriptional bursting is a major source of noise in gene expression. The telegraph model of gene expression, whereby transcription switches between on and off states, is the dominant model for bursting. Recently it was shown that the telegraph model cannot explain a number of experimental observations from perturbation data. Here we study an alternative model that is consistent with the data and which explicitly describes RNA polymerase recruitment and polymerase pause release, two steps necessary for mRNA production.

In various biological processes such as endocytosis and caveolae formation, the cell membrane is locally deformed into curved morphologies. Previous models to study membrane morphologies resulting from locally induced curvature often only consider the possibility of axisymmetric shapes—an indeed unphysical constraint. Past studies predict that the cell membrane buds at low resting tensions and stalls at a flat pit at high resting tensions. In this work, we lift the restriction to axisymmetry to study all possible membrane morphologies.

Upon nitrogen starvation, Schizosaccharomyces pombe exit mitotic cell cycle and become irreversibly committed to the completion of meiosis program. Meiotic cell divisions are coordinated with sporulation events to produce haploid spores. In the last few decades, experiments on fission yeast have revealed different molecular players involved in two meiotic cell divisions, MI and MII. How the MI entry, MI to MII transition, and MII exit occur due to the dynamics of the regulatory network is not well understood.