Intrinsically disordered domains essential for membrane-shaping proteins

In living cells, the shape of various internal membrane structures is controlled by curvature-inducing proteins. Some proteins form membranes into spherical shapes, while others, such as the Bin/Amphiphysin/Rvs (BAR) superfamily of proteins, create tubular membrane structures using crescent-shaped binding domains.

Recent experiments, however, have shown that BAR proteins shape membranes not just with their crescent-shaped ordered domains, but also with a collection of intrinsically disordered domains. Hiroshi Noguchi developed a numerical simulation to study the interplay between ordered and intrinsically disordered domains in BAR proteins.

In BAR proteins, intrinsically disordered domains take the form of long, flexible strings that extend outward from the core protein. Because they have no fixed shape, these domains are often dismissed. Many in vitro experiments remove them to study the interactions between ordered domains and membranes, assuming the effect from disordered domains is small. A few experiments, however, have challenged that assumption.

“Recent experiments showed clear effects of the disordered domains,” said Noguchi. “However, the detailed interactions are difficult to experimentally investigate. Coarse-grained simulations are the best methods for this scale.”

Noguchi found that disordered domains generate a repulsive force between them, which leads to several structural changes in surrounding membranes as the proteins separate. In flat membranes, for instance, intermediate-length domain strings lead to many small tubules, while longer domain strings force the proteins even further apart and lead to fewer, but much longer, tubules.

“The disordered domains have been underestimated,” said Noguchi. “I hope that researchers consider their effects more.”

Source: “Membrane shape deformation induced by curvature-inducing proteins consisting of chiral crescent binding and intrinsically disordered domains,” by Hiroshi Noguchi, Journal of Chemical Physics (2022). The article can be accessed at https://doi.org/10.1063/5.0098249 .